Nanoarchitectonics beyond perfect order – not quite perfect but quite useful

Abstract

Nanoarchitectonics, like architectonics, allows the design and building of structures, but at the nanoscale. Unlike those in architectonics, and even macro-, micro-, and atomic-scale architectonics, the assembled structures at the nanoscale do not always follow the projected design. In fact, they do follow the projected design but only for self-assembly processes producing structures with perfect order. Here, we look at nanoarchitectonics allowing the building of nanostructures without a perfect arrangement of building blocks. Here, fabrication of structures from molecules, polymers, nanoparticles, and nanosheets to polymer brushes, layer-by-layer assembly structures, and hydrogels through self-assembly processes is discussed, where perfect order is not necessarily the aim to be achieved. Both planar substrate and spherical template-based assemblies are discussed, showing the challenging nature of research in this field and the usefulness of such structures for numerous applications, which are also discussed here.

---

Lin Cao

Lin Cao received her M.S. degree in Food Science and Engineering from the National Engineering Research Center of Seafood, Dalian Polytechnic University, China. She is currently pursuing a Ph.D. degree in the Biotechnology faculty at Ghent University, Belgium. Her research interests include the synthesis of nanomaterials and organic-inorganic hybrid hydrogels with applications in biology and food science including functional compound target delivery, drug delivery, and tissue engineering.

Yanqi Huang

Yanqi Huang received his M.S. degree in Powder Metallurgy Research from Central South University, China. He is currently pursuing his Ph.D. degree in the Biotechnology faculty at Ghent University, Belgium. His research interests include the synthesis of nano-inorganic materials and hydrogels with applications in biology including drug delivery systems and tissue engineering.

Bogdan Parakhonskiy

Bogdan Parakhonskiy received his Ph.D. from Lomonosov Moscow State University, Russia in 2009. He held a Marie Curie Postdoc fellowship at the University of Trento, Italy. After this, he worked as a group leader in the theranostic laboratory at Saratov State University, Russia. Since 2015 he has been the holder of a prestigious FWO (Flanders Research Foundation) fellowship at Ghent University, Belgium. His research interests focus on the design and modification of composite scaffolds and colloidal particles, biomineralization, and drug delivery. He is a pioneer in the development of carriers such as calcium carbonate particles, hydrogel matrices, and capsules.

Andre G. Skirtach

Andre Skirtach was born in Ukraine and received an MSc degree in Physics from Lomonosov Moscow State University, Russia, and a Ph.D. degree in Chemistry from McGill University, Canada. Subsequently, he joined the National Research Council of Canada (NRC) in Ottawa. In 2000, Dr Skirtach and colleagues were involved in establishing a prominent startup—Trillium Phot., Inc. He then moved to the Max Planck Institute of Colloids and Interfaces, Golm, Germany, first working as a researcher and then as a Group Leader. In 2011, Dr Skirtach joined the Faculty of Bioscience Engineering, Ghent University, Belgium. His scientific research interests include nanotechnology and nanobiotechnology, cell biology, cell death and mechanobiology, development of microscopy and analytical methods, nanoparticles, polymeric capsules and planar interfaces, self-assembly and its applications.

---

1. Introduction

While it exists at different size scales, such as macro-, micro-, and atomic or sub-nano, architectonics at the nanoscale, or nanoarchitectonics, is the focus of our analysis here. Historically, the early roots of architectonics can be linked to Aristotle, who put practical craftsmanship and the concept of technē in contrast to the more abstract thoughts of his teacher, Plato.¹ Later on, architectonics can be traced to Kant who, however, developed its more abstract perception, in contrast to the directly related terms “man the knower”, “man the doer”, and “man the maker” of Aristotle. Even cellular sub-structures, composition, and anatomy have been linked to the term architectonics, albeit as cytoarchitectonics.² In biomedicine, the term architectonics can have specificity, depending on the application area: for example, it was linked to microscopic and larger-scale organs in the neurosciences.³ Furthermore, architectonics can be linked to the construction and design of buildings. The sheer scale of building blocks in architecture enables the construction of buildings exactly according to projected design, and the same holds true for micro-architectonics due to the sizes of building blocks and advances in the microstructural sciences, particularly in the last century when microstructural sciences were quickly developing. Curiously, and as was insightfully reported by Ariga (NIMS, Japan) and co-workers, similar correspondence exists both at the micro- and atomic scales, where in the former case the geometrical factors eliminate the influence of molecular forces, while at the atomic scale, the interaction between atoms leads to a specific lattice arrangement or molecular structure.⁴ This does not necessarily hold true at the nanoscale due to molecular forces acting on the building blocks, predominantly molecules and nanoparticles. The attractiveness of applications in energy,^5,6 environmental,^7,8 and biomedical issues^9,10 propelling development in the area of nanoarchitectonics is discussed complementary to earlier description.¹¹

Fabricated nanomaterials often exhibit unique physical and chemical properties due to their high surface area and nanoscale size (at least one dimension measuring 100 nm or less).¹² Top-down nanomaterial synthesis approaches have been extensively studied, incorporating metal nanoparticles,^13,14 inorganic nanoparticles,¹⁵ nano aerogels,¹⁶ nanofibers,¹⁷ and so on, which have been applied in the corresponding fields. However, functional nanomaterials with a rational organization cannot be directly created only by nanotechnology-related top-down approaches,¹⁸ because the regulation of nanoscale components and structures is becoming crucial to the future of nanotechnology. In this context, bottom-up strategies based on self-assembly create well-considered materials by controlling the arrangement of atoms,¹⁹ molecules,²⁰ macromolecules,²¹ or supramolecules,²² and have lately received great attention. These bottom-up self-assembly processes are similar to an ideal biological system for fabricating high-performance materials with incredibly high efficiency, selectivity, and multifunctionality.¹⁸ Overall, the types of self-assembly can be classified into static, dynamic, templated and biological self-assembly, and in self-assembly often the static type is used.²³

The concept of nanoarchitectonics was originally proposed by Masakazu Aono in 2000.^24,25 The term is supposed to be a novel technology system for the production of new functional materials from nanoscopic building blocks through harmonization of various processes, including atomic/molecular manipulation, chemical nanofabrication, self-assembly/organization, field-regulated organization, and bio-related treatments.^26–28 Nanoarchitectonics represents a next-generation methodology that combines solid knowledge of nanotechnology with various other scientific disciplines such as supramolecular chemistry,^29,30 organic/polymer synthesis,^31,32 physical materials control,³³ and biological materials conversion and organization.^34,35 Driven by the extensive efforts of Ariga, nanoarchitectonics has been diversified and the range of applications extended.^24,25,28,36 For example, functional building blocks such as conductive polymers, hydrogels, and ionic polymers have been prepared for application in smart energy supercapacitors due to their excellent electrochemical performance.³⁷ The co-assembly of peptides and other bioactive components has become a facile strategy to form nano-structural units to achieve targeted release in tumor supramolecular nanotheranostics.³⁸ It can be noted that the major difference between nanoscopic material synthesis and macroscopic manufacturing originated from various uncontrollable uncertainties such as thermal fluctuations, quantum effects, statistical distributions, and ingenious mutual interactions, which cannot be ignored in the nanoscale system.¹⁸ Therefore, actions and interactions in the nanoworld have to be coordinated rather than simply being summed up.⁴ It should be noted that analytical techniques, or more specifically nano-scale imaging, are of paramount importance for the development of nanoarchitectonics. That is why recent developments in high-resolution imaging employing, for example, scanning tunneling microscopy (STM), transmission and scattering electron microscopy (TEM and SEM), cryo-electron microscopy, and atomic force microscopy (AFM), which allow observation and manipulation of nanoscale materials, have deepened our understanding of nanoarchitectonics. In general, it can be also noted that assembled structures can be defined as those with perfect (high) order and those without perfect (low) order. The former (i.e. perfect, or what can be referred to as a high order) category can be further sub-divided into structures without defects and those with some (typically minor) defects; however, both types of such structures would have a distinct and repeatable pattern.³⁹ The latter type of structure (with imperfect or low order) typically lacks a specific pattern.^40,41

In this review, we analyze developments in nanoarchitectonics looking at structures assembled without perfect order, which can be empirically divided into polymer brushes, layer-by-layer (LbL) assembly, and hydrogels. Such assemblies contrast with those in which perfect order of constituent elements can be obtained, such as structures in self-assembly with perfect order, Fig. 1. In that regard, nanoarchitectonics is different from architectonics, micro-architectonics, and atomic scale, sub-nano architectonics, where design precisely follows the projected structure. We also analyze various applications in biomedical fields, where such assemblies are useful.

Fig. 1 (A) Schematics of architectonics at different size scales.⁴ Grey areas are not covered by this article. (B) Degree of the order of different assembly modalities. Reproduced with permission from ref. 4. Copyright © 2015, Wiley.

2. Self-assembly structures with perfect order

Self-assembly refers to the organization of components into patterns or structures without external intervention;²³ it is ubiquitous from macro- to micro-scale, and it is different from positional assembly where the permutation and combination of molecules are controlled artificially, but which largely depend on the characteristics of molecules and the non-covalent interactions.⁴² The above actions enable molecules to form specific organizations and be located at appropriate positions without external forces and to eventually spontaneously form ordered, rational, and many other useful structures. Notably, such non-covalent binding forces are not as strong as covalent bonds (400 kJ mol⁻¹), making the system more flexible and allowing the reversibility and dynamics of self-assembled nanostructures to be maintained. Molecular units involved in self-assembly range from the nanoscale, and allow one to program materials at the nanoscale to achieve desired structures and properties. These superiorities render the technology important in nanotechnology, from chips to electric vehicles to performance optimization of biomaterials. Assembly at the nanoscale is a highly versatile methodology for establishing nanoarchitecture functional systems from a variety of small units. Self-assembly is mainly driven by various weak and reversible non-covalent interactions including hydrogen bonding, van der Waals interactions, electrostatic interactions, hydrophobic interactions, and π–π stacking. To go further, the construction of functional materials from nanoscale building blocks also calls for essential contributions from non-nanotechnology areas such as supramolecular chemistry with self-assembly/self-organization, materials fabrications, and biotechnology. Therefore, based on self-assembly, to further develop a way to control and modulate interactions within nanostructures, nanoarchitectonics, a progressive and novel concept, has emerged as a research paradigm alongside nanotechnology.

In general, one can distinguish self-assembly in: (a) nature,⁴³ (b) colloids and nanoparticles,⁴⁴ (c) mixed nanoparticle/polymer mixtures,⁴⁵ and (d) molecular systems.⁴⁶

(a) Self-assembly in nature. Over the past two decades, the principles of self-assembly in nature have inspired materials scientists to explore the fabrication of artificial materials with hierarchical structures and tailored properties, and to create functional devices. The self-assembling building blocks of peptides and nucleic acids bound to a variety of ligands perform intricate and diverse dynamic functions, and have been recognized as an outstanding family of structural units for the bottom-up fabrication of complex nano-biomaterials.^43,47 The interactions relevant in nature's self-assembly are noncovalent forces including electrostatic interactions, hydrophobic effects, van der Waals interaction, hydrogen bonding, metal coordination and aromatic stacking, rather than covalent bonds. Incorporating self-assembly from nature into existing nanotechnology can offer new possibilities for the creation of reproducible hierarchical biomaterials with precise biomolecular and physical properties.⁴⁸

(b) Colloidal self-assembly. An ensemble of colloidal nanocrystals can be led to self-assemble into an ordered superlattice driven by, for example, evaporation-based nanocrystal self-assembly,⁴⁹ destabilization-based nanocrystal self-assembly,⁵⁰ kinetics of nanocrystal self-assembly,⁵¹ and hydrocarbon-capped nanocrystal.⁵² The complex phase behavior and the flexibility of superlattice composition and structure suggest that controlled nanocrystal self-assembly could be an important enabler of next-generation materials design.⁴⁴ Organic surfactants optimized for nanocrystal synthesis are also well suited for ordering nanocrystals into superlattices. Moreover, the effective nanocrystal size and shape can be achieved by modifying nanocrystal surfaces after synthesis. Self-assembly driven by chemical processes at the nanocrystal surfaces leads to a partial desorption of native hydrocarbon ligands,⁵³ homopolymer surface ligands,⁵⁴ block copolymer surface ligands,⁵⁵ coarse-grained models for ligand-tethered nanocrystals,⁵⁶ capping layers containing two or more ligand species as patchy particles,⁵⁷ charged aliphatic surface ligands and charged nanocrystal cores,⁵⁸ DNA-based surface ligands,⁵⁹ toward biologically inspired self-assembly,⁶⁰ and molecular switches as surface ligands.⁶¹ Self-assembly of nanocrystals can also make use of physical processes such as temperature,⁶² pressure regulation of interparticle coupling,⁶³ template and structure,⁶⁴ and external forces (electric/magnetic fields or fluid flows), but these processes do not extend to serial manipulation of building blocks (e.g., dragging individual particles into position).⁴⁴

(c) Self-assembly in nanoparticle/polymer systems. For individual nanoparticles or polymers, the hydrophobic interactions of nanoparticles are capable of inducing nanoparticles into clusters with well-controlled sizes and interparticle distance;⁶⁵ self-assembly of block copolymers is an unique approach for surface patterning with ordered structures.⁶⁶ The synergistic interactions between self-organizing particles and a self-assembling matrix material can also lead to hierarchically ordered structures.⁴⁵ One approach is to synthesize inorganic nanoparticles within the microdomain of well-ordered block-copolymer templates.⁶⁷ Another approach is using the self-assembled micro-domain morphology of block copolymers to control the spatial arrangement of nanoscopic elements within the materials.⁶⁸ These novel hybrid materials provide a means of controlling electrical, magnetic, or optical properties.⁶⁹

(d) Molecular systems. In the field of molecular architectonics, different approaches are used. For example, biorecognition is often used as an effective method to construct novel supramolecules. Flexible control of the aspect ratio, higher-order layering, and ordering of self-assembled systems can be achieved by design and engineering development, combination and stepwise advancement of desired single molecules or modules at different scales and dimensions. In addition, the inherent multivalency of the assembled structure generally allows for more efficient biological effects and higher local concentrations of given chemical signals. At present, a large number of self-assembly systems based on inorganic nanoparticles, and organic substances including polysaccharides, peptides, proteins, and mixtures have been applied to drug delivery, biological scaffolds, and biosensing systems for regenerative tissue engineering, due to their multifunctional potential, biocompatibility, scalability, and tunability. Numerous self-assembly systems with perfect structures such as Langmuir–Blodgett (LB), lipid assembly, evaporative self-assembly, and templated self-assembly have been summarized, and the most typical structures are LB and lipid assembly.

In the past few decades, low-dimensional nanomaterials with low-level ordered structures have been prepared by means of film coating, solvent evaporation, and capillary forces, but their regularity, ordering, and controllability still require greater improvement. Driven by self-assembly technology, researchers discovered that LB technology can precisely control the molecular arrangement and assembly at the nanoscale. LB film is achieved by dispersing both hydrophilic and hydrophobic molecules at the gas–liquid interface, gradually compressing the volume occupied by the water surface, and finally transferring the film from the gas–liquid interface to the immersed solid matrix to obtain a Langmuir membrane with a monolayer arrangement⁷⁰ (Fig. 2A and B). It is an ordered interfacial self-assembly technique on the substrate, and the film can be composed of single or multilayers of organic materials, and each dipping or reproduction step can uniformly adsorb the monolayer. In this way the thickness of the film can be precisely controlled, providing possibilities for the eventual realization of highly ordered, well-defined, controllable single/multilayer structures.⁷¹ Structures used in the process include liposomes, nanoparticles, polymers, proteins, and biomolecules, and this perfect structure has potential applications in semiconductor fabrication,⁷² supramolecular chemical media,⁷⁰ and biotechnology.⁷³ Besides, a perfect phospholipid bilayer structure was shown to be formed by a spontaneous orderly arrangement of the hydrophilic heads and hydrophobic tails of phospholipid molecules through the investigation of the structure of biological membranes. This kind of bilayer is the most important structure ubiquitous in living organisms and the best representative type of self-assembly technology in nature. Liposomes are spherical vesicles which possess a closed structure formed by the self-assembly of phospholipids in aqueous solutions (Fig. 2C). The driving force for this process is derived from the hydrophobic effect, which in turn organizes the amphiphilic phospholipid molecules to reduce unfavorable interactions between the hydrophobic acyl chains and the surrounding aqueous medium.⁷⁴ This effect is triggered by various intermolecular forces including electrostatic interactions, hydrogen bonding, van der Waals, and dispersion forces.⁷⁵ Importantly, similarity of the composition of liposomes and biological membranes endows the former good biocompatibility, while their amphiphilic structure enables them to load various hydrophilic and hydrophobic therapeutic drug molecules with favorable loading efficiency.⁷⁶ Liposomes also allow modification of the surface by a variety of different chemical groups to obtain stimuli-responsive and smart properties, which ultimately guarantee targeted and controlled drug release.⁷⁶ The encapsulation performance of liposomes can be enhanced by the increment of drug solubility and stability, which play a positive role in achieving sustained drug release and improving drug efficacy. More attractively, their subcellular size allows relatively high intracellular uptake and enhances bioavailability of drugs in vivo.⁷⁷ However, liposomes are susceptible to rapid clearance during the transportation process in blood because of the adsorption of second-generation plasma proteins, although polymer coatings can effectively overcome this issue and maintain good pharmacokinetic properties of liposomes.^78,79 In addition, the circulatory half-life of liposomes can be modulated by changing the composition of the lipid bilayer.⁸⁰ In brief, the membrane-like composition and high-level orderly structure of liposomes promote their extensive application in medical fields, such as drug delivery vehicles, vaccination adjuvants, signal enhancers, or carriers with a focus on medical diagnostics and analytical biochemistry, and support matrices for various components.⁸¹

Fig. 2 An illustration depicting the compression of a Langmuir–Blodgett film (A) by moving a barrier across the surface of a liquid covered by loosely packed amphiphilic molecules.⁸¹ (B) When fully compressed, the monolayer can be transferred to a substrate by a number of techniques including dip coating.⁸² (C) Schematic of the general structure of liposomes.⁸³ Reproduced with permission from ref. 81 and 82. Copyright © 2014, Tsinghua University Press and Springer; and Copyright © 2021, Elsevier.

3. Nanoarchitectonics beyond perfect order: polymer brushes, LbL assembly, hydrogels, and other structures

Opposite to perfect (high order) structures^84,85 which are without defects (Fig. 3A and B) or with minor defects (Fig. 3C and D), self-assembled nanostructures with imperfect (low or no) order and alignment are still often overlooked and even neglected, but this type of structure includes a broad range of nanomaterials, for example, those with an irregular crosslinking^86,87 (Fig. 3E and F), those that are porous⁸⁸ (Fig. 3G) and of uneven thickness⁸⁹ (Fig. 3H). Nevertheless, non-perfect self-assembly of nanostructures is sufficient for control and thus to achieve their function.^90,91 A summary of some of these structures, materials and interaction forces is presented in Table 1.

Fig. 3 (A) TEM image of films with long-range ordered quantum dot superlattices.⁸⁵ (B) (100) plane of cubAB₁₃ type binary nanoparticle superlattices formed by 8.1 nm CdTe and 4.4 nm CdSe nanocrystals.⁹² (C) TEM image of an array of Au colloidal nanocrystals (Au NCs) capped with dodecanethiol.⁸⁴ (D) SEM patterns of mesostructures of 5.7 nm cobalt nanocrystals having 13% size distributions subjected to a magnetic field perpendicular to the substrate during the evaporation time.³⁹ (E) Surface SEM images and (F) cross-sectional SEM images of graphene oxide-polydimethyl diallyl ammonium chlor-hydrolyzed PVDF (GO-PDDA-h-PVDF) membrane.⁸⁶ (G) SEM micrograph of hierarchical porous chitosan cryogels.⁸⁸ (H) SEM image of glass coated with 20 bilayers of chitosan/carboxymethylcel complex.⁸⁹ Perfectly self-assembled order (top) and imperfect self-assembled structures (bottom). Reproduced with permission from ref. 39, 84–86, 88, 89 and 92. Copyright © 2016, American Association for the Advancement of Science; Copyright © 2010, American Chemical Society; Copyright © 2009, American Association for the Advancement of Science; Copyright © 2007, American Chemical Society; Copyright © 2020, Elsevier; Copyright © 2018 Taylor & Francis; and Copyright © 2018, Elsevier.

Table 1 Summary of basic properties of polymer brushes, LbL assembly, hydrogels and other structures

	Materials	Forces	Morphology	Properties	Ref.
Polymer brushes	Polymer single-crystal sheets + poly(ε-caprolactone) + glass substrate	Chemical coupling	Irregular chain-folding	Super-density	108
		Hydrogen bond
	Diblock copolymers (liquid-crystalline polymer + polystyrene)	Electrostatic interaction	—	High-density	277
	Block copolymers (polystyrene + polylactide)	Electrostatic interaction	Gyroid-like	Potential responsive feature, capture and release properties	112
LbL assembly	Quantum dots (CdSe, CdZnS, CdTe, AuNPs, CdS, ZnS, MoS2, and carbon quantum dots)	Electrostatic interaction	Spherical/nanoflake-shaped/undulations and rough surface	Transparency^151	151, 152, 278 and 279
				Ammonia-sensing^152
				Photoelectrochemical and photocatalytic^278
				Long-term stability and anti-fouling^279
	Polyelectrolyte polymers (poly(3-aminobenzylamine), poly(sodium 4-styrenesulfonate), poly(acrylic acid), poly(ethylene oxide)-block-poly(ε-caprolactone), polydopamine, poly-L-lysine, polysaccharides, proteins, poly-amino acids, and tannic acid)	Electrostatic interaction	Spherical/undulations and rough surface/porous	Dopamine-sensing^154	154–156, 158, 167, 280 and 281
		Hydrogen bond		Stimulated-release^156
				pH-Responsive^158 and antimicrobial effect^156,167
				Enhanced biological properties^158
	Inorganic nanoparticles (SiO2, titanium, alumina, CaCO3, carbon, and magnetic iron oxide) + polyelectrolyte layers (poly(allylamine hydrochloride), poly (diallyldimethylammonium chloride), polysaccharides, proteins, poly(ε-caprolactone), and poly-amino acids)	Electrostatic interaction	Porous/spherical/irregular-shape/undulations and rough surface	pH-Sensitive^172,174	172–174, 176, 178, 190, 272 and 282–284
				Improve cells growing^173,272
				Sensitive to bacteria composition^282
				Antimicrobial activity^176
				Drug loading^190
				Cancer cell killing^283
Hydrogels	Natural polymer (polysaccharides, and poly peptide) + substrate (silicon wafers, glass substrates, and titanium)	Electrostatic interaction	Porous/undulations and rough surface	pH-Triggered programmable deformations and sequential double folding behavior^222	222, 226 and 227
		Hydrogen bond		Resisting bacterials^227,228
				Attracting cells^228
	Natural polymer (polysaccharides, poly peptide, proteins, and DNA)	Electrostatic interaction	Porous/spherical/ellipsoid/nanofiber/undulations and rough surface	Stimulated-release^285	236, 245, 249, 285 and 286
		Hydrogen bond		Controlled stiffness and shearing-respondent^245
				Enhanced cell proliferation^286
Other structures	Semiconductor, metal, magnetic particles, and nanocrystals	Hydrophobic	Mostly flat substrates	Responsiveness to different stimuli (light, magnetic, temperature, etc.)	275, 276 and 287–289
		Magnetic
		Steric
		Acoustic levitation

---

Although the molecular arrangement or the morphology is imperfect in these materials, they are often used to address important issues and challenges, and it is worthwhile devoting effort to further explore their potential for nanoarchitectonics. In this regard, construction of functional self-assembled materials into thin films and coatings is essential for further expansion of the range of their applications, as they often control and even dictate interactions with the surrounding environment. More specifically, polymer brushes, hydrogels, LbL assembly, and other structures offer effective means for coating substrates with polymers, colloids, and biomolecules. Notably, thin film nanoarchitectonics can be an outstanding archetype for total three-dimensional (3D) nanoarchitectonics. Preparation of raw materials based on nanoscale self-assembly is an anticipated key concept for acquiring new functional materials, while constructing whole 3D structures at the nanoscale remains a difficult task even with currently existing technologies.⁹³ The design of 3D structures is based on an extension of two-dimensional (2D) architectures, where a particular flexibility of the LbL self-assembly has been extensively used. Furthermore, hydrogels have been emerging in 3D nanoarchitectonics due to their controllability, for example by particles, mechanical performance, and versatility of design capabilities. Further controllable construction of 3D nanoarchitectonics similar to internal units of biological systems will greatly promote the progress of biomedical applications.

Here, we present an overview of recent developments in self-assembly research with special attention paid to examples of the construction of non-perfect hierarchical functional structures involving inorganic nanoparticles, organic molecules or hybrid structures.⁹⁴ In particular, 2D nanoarchitectonics for surface adsorption including polymer brushes, LbL planar coatings and hydrogel films as well as 3D nanoarchitectonics including LbL particles and hydrogels are summarized. Some other structures with imperfect assembly are also highlighted and major strategies for preparing all these nanomaterials are discussed. Furthermore, we describe several application areas of 2D and 3D nanoarchitectonics assemblies using polymer brushes, LbL, hydrogels, and other structures in biomedicine, tissue engineering, drug delivery, and therapeutics. Finally, we provide an outlook describing potential applications and development steps of nanoarchitectonics for materials based on imperfectly assembled structures.

3.1 Polymer brushes

Over the past few decades, self-assemblies of polymer brushes, including homopolymer, block-copolymer, and mixed-polymer brushes, have invoked great interest in the fields of chemistry and materials science. Polymer brushes are special macromolecular structures wherein one end of the polymer chain is densely tethered to the surface of a planar matrix and the other end is stretched owing to the excluded volumetric repulsion.^95–97 The introduction of polymer chains onto solid surfaces not only significantly changes the surface-related properties but also endows the obtained polymer brushes with exquisite properties such as adhesive behavior, colloidal stability, corrosion protection, stimuli-responsiveness, lubrication, friction properties, and so forth.⁹⁸ Generally, polymer brushes can be synthesized using different strategies: physical adsorption,⁹⁹ “grafting to”,¹⁰⁰ and “grafting from”¹⁰¹ or “grafting through”¹⁰² strategies (Fig. 4). Physical adsorption is a reversible process involving the self-assembly of macromolecules with appropriate blocks of functional groups interacting with the groups on the surface.¹⁰² The “grafting to” approach is achieved by directly grafting pre-synthesized polymer chains to a substrate under efficient coupling reactions or specific interactions. In the “grafting from” method, polymer chains grow from the surface-immobilized initiators or RAFT agents to produce polymer brushes.¹⁰³ Given the effects of the aggregation state of polymer chains and intermolecular steric hindrance on the properties of polymer brushes, “grafting from” displays less steric hindrance than “grafting to” to obtain polymer brushes with a relatively high grafting density and longer polymer chains. The “grafting through” strategy is a combination of “grafting from” and “grafting to” to create chains of macromolecules simultaneously in a solution and on a surface during the synthetic procedure. The lateral structures in polymer brushes depend on the relative lengths of building blocks and the energies of their interactions with each other and the solvent. The densely grafted macromolecules can self-assemble into hexagonally arranged micelles, inverse micelles, and stripes consisting of outer blocks;¹⁰⁴ nevertheless, not densely grafted macromolecules would form “onion-like” and “garlic-like” micelle structures with the cores of less soluble blocks surrounded by more soluble blocks,¹⁰⁵ or a “flower-like” micelles with dense cores and loose “petals”.¹⁰⁶ With the great development of polymer materials, organic and inorganic chemistry, supramolecular chemistry, and various living/controlled polymerization methods have been employed in the fabrication of polymer brushes with control or optimization of composition, architecture, and the length of polymer chains.¹⁰⁷ However, polymer brushes without perfect constructions still demonstrate functionality. In the following part, polymer brushes with random structures prepared by the self-assembly of macromolecules and self-assemblies of polymer brushes are the focus of discussion.

Fig. 4 Major strategies of fabrication of polymer brushes: (A) physical adsorption of macromolecules, (B) “grafting to”, (C) “grafting from” and (D) “grafting through” methods.¹⁰² Reproduced with permission from ref. 102. Copyright © 2021, The authors, published by Elsevier.

Physical adsorption is a facile and straightforward method employing hydrogen bonds, van der Waals, or electrostatic interactions.¹⁰² Brandani and co-workers investigated the adsorption and desorption behavior of triblock copolymers on a self-assembled hydrophobic surface.⁹⁹ The presence of polymer brushes was revealed by AFM. Nevertheless, this self-assembly-based approach cannot lead to desired dense and thick brushes, and a combination of self-assembly and other methods would be required. Zhou and co-workers reported a self-assembly-assisted grafting-to approach to synthesize polymer brushes on flat substrates.¹⁰⁸ In this study, polymer chain ends were functionalized by an alkoxysilane group and pre-assembled into 2D polymer single crystals (PSCs). Chemically coupling the PSCs onto solid substrates led to the formation of polymer brushes with a grafting density as high as 2.12 chains per nm². Moreover, polymer loop brushes can be obtained using oddly folded PSCs with bi-functionalized chain end (Fig. 5A). They provided a new pathway for synthesizing super-dense polymer brushes which are promising for various fields.

Fig. 5 (A) Synthetic route for polymer brushes via the self-assemble assisted-grafting-to method.¹⁰⁸ (B) Schematic illustration of polymer grafting to the substrate.¹⁰⁹ TEM images of the triblock copolymer (C) and diblock copolymer (D) micelles and their corresponding illustrations.¹⁰⁹ Reproduced with permission from ref. 108 and 109. Copyright © 2016, The authors; and Copyright © 2020, The Royal Society of Chemistry.

Self-assemblies of polymer brushes play an important role in fully realizing their functionalities. Grafting polymer brushes on inorganic plates is an example inspired by the adhesive nature of mussels and the antifouling properties of zwitterions. For example, Zhai and co-workers designed amphiphilic ABA triblock and AB diblock copolymers on silicon wafers, where A was a catechol-anchoring and B was a hydrophilic zwitterionic block.¹⁰⁹ Amphiphilic block copolymers consisting of a hydrophilic poly[(sulfobetaine methacrylate)-co-(2-(dimethylamino) ethyl methacrylate)] (P(SBMA-co-DMAEMA)) block and a hydrophobic poly(dopamine methacrylamide) (PDMA) block are capable of self-assembling into star-like micelles and flower-like micelles due to the hydrophobic interactions in aqueous diblock and triblock copolymer solutions, respectively (Fig. 5B). TEM images showed that the micelles of self-assemblies of triblock copolymer and diblock copolymer were not uniform in size (Fig. 5C and D). The triblock polymer-coated surfaces showed excellent protein-reduction performance over diblock copolymer-coated surfaces at the same polymer concentration, which exhibited better antifouling properties. The force-versus-separation curves revealed that the loop conformation of triblock copolymers was attributed to an enhanced steric stabilization of the surface, and the loop conformation is probably the reason for improved protein-resistance capability. Thermo-responsiveness is another important property of polymer brushes.¹¹⁰ What's more, brushes can be made not only on flat surfaces but also on elongated structures, like microtubules, which provides new possibilities for the design of functional materials.¹¹¹

Although the use of self-assembly methods for the synthesis of polymer brushes is not very common, the self-assembly behavior of polymer brushes is the key to a reliable design of functional 3D polymer materials. For example, block-type diblock molecular polymer brushes (MPBs) with polystyrene (PS) and polylactide (PLA) compartments were incorporated into surfactant-stabilized oil-in-water emulsions, and the MPBs formed solid nano/microparticles through self-assembly due to the increasing confinement in the nano-emulsion droplets during solvent evaporation.¹¹² The self-assembly properties of MPBs have been used in a variety of different applications such as nanofabrication, cellular imaging and even mimicking complex biological functions such as size- and charge-selective molecular transport.¹¹³

3.2 LbL self-assembly of nanostructures

LbL assembly built by deposition of alternately charged polyelectrolyte multilayers provides significant benefits to the generation of functional materials.^114–117 LbL assembly is a powerful technique for preparing multilayer films and coatings,^118,119 allowing the application of various stimuli to control the nanoscale thickness of overall films and the composition of hierarchical materials.^120–122 The LbL assembly process is often driven by electrostatic interactions, i.e., charge neutralization and re-saturation of the counterionic component materials upon adsorption onto the charged surface resulting in a charge reversal.^123–125 This permits alternate adsorption of cationic and anionic polyelectrolytes at a surface.¹²⁶ Besides, hydrogen-bonding interactions,^127–129 bio-specific interactions,¹³⁰ charge transfer interactions,¹³¹ electrochemical reactions,¹³² metal coordination,¹³³ stereo-complex formation,¹³⁴ sol/gel reactions,¹³⁵ molecular interactions,¹³⁶ or covalent bonding formation¹³⁷ can also act as driving forces of LbL assembly. Another property of LbL assembly is pH-,^138–141 salt-,^142,143 redox,¹⁴⁴ ionic strength¹⁴⁵ responsiveness, and crosslinking capability.¹⁴⁶ LbL assembly exhibits the unique characteristics of facile and inexpensive procedures, which can be divided into three mature operational strategies. Conventionally, multilayer nanoarchitectures would be obtained on a planar substrate by simply immersing the substrate into solutions for depositing layered materials¹¹⁴ (Fig. 6A). Further, spray- and spin-coating-assisted LbL assemblies, which benefit from industrial spin-coating equipment, have been developed for LbL processing in recent years^36,147,148 (Fig. 6B and C). These innovative methods have been proved to form LbL films in sub-second to second time intervals per layer instead of traditionally used immersion adsorption steps which take several minutes. Different methods can result in differences in the stratification versus interpenetration of the layers that should be considered when designing films for different applications. Compared with the LB technique, which produces tightly arranged and well-defined ordered monolayers, the LbL approach generates quite flexible and non-crystalline multi-component assemblies. LbL-assembled materials often contain structural and morphological variations or even defects that hinder the formation of grain boundaries, which in turn are favorable for the facile diffusion of small molecules and open possibilities for dynamic functions. These imperfect features are highly advantageous for sequential nanoreactors, protective coatings, and drug delivery systems.¹⁴⁹

Fig. 6 Schematic illustration of the LbL assembly process with (A) dipping method, (B) spray deposition method,³⁶ and (C) consecutive spin-coating method.¹⁴⁷ Reproduced with permission from ref. 36 and 147. Copyright © 2022, The Owner Societies; and Copyright © 2016, The Royal Society of Chemistry.

3.2.1 LbL self-assembly of 2D nanostructures on substrates. Noble metal and semiconductor nanoparticles exhibit remarkable electronic and optical properties that are strikingly different from those of their bulk materials.¹⁵⁰ These inorganic nanoparticles were deposited onto substrates by LbL self-assembly techniques to produce functional films, which have a wide range of applications in sensing. Lu and co-workers created nanoarchitectonics structures consisting of hydrophobic CdSe/CdZnS quantum dots (QDs) and hydrophilic CdTe and Au nanoparticles (AuNPs), linked by a functional silica layer on a slide glass.¹⁵¹ SEM images of AuNPs films and CdSe/CdZnS core/shell QDs films demonstrated that AuNPs or CdSe/CdZnS cannot be dispersed well in the slide glass at high concentration, and uneven aggregation occurred. TEM imaging of CdTe QDs films revealed similar results to those obtained for AuNPs films and CdSe/CdZnS core/shell QDs films. But these glass films are also promising for applications in biomedicine and clinical diagnostics due to their excellent stability and transparency. Zhang and co-workers first fabricated a molybdenum disulfide (MoS₂)/tricobalt tetraoxide (Co₃O₄) nanocomposite film sensor on a substrate with interdigital electrodes via the LbL self-assembly route¹⁵² (Fig. 7A). The surface morphology of as-prepared Co₃O₄, MoS₂, and MoS₂/Co₃O₄ film was examined by SEM. Fig. 7B shows that the shapes of hydrothermally synthesized Co₃O₄ nanorods are not identical, and the size distribution is between 65 and 135 nm. On the other hand, MoS₂ has a nanoflake-shaped structure, and its size distribution extends from 110 to 290 nm. In the MoS₂/Co₃O₄ nanocomposite, Co₃O₄ nanorods and MoS₂ nanosheets were in contact with each other without strict arrangement. The sensing performances of the MoS₂/Co₃O₄ nanocomposite film sensor were evaluated by exposure to an ultra-low concentration of ammonia gas in the range of 0.1–5 ppm at room temperature. The experimental results revealed that imperfectly structured films possessed a high sensitivity, good repeatability, stability, selectivity, and fast response/recovery characteristics for NH₃. Rodrigues and co-workers assembled LbL films of oppositely charged polymer-stabilized graphene layers as (GPDDA/GPSS)₁₀, also including gold nanoparticles (AuNPs) in another architecture ((GPDDA/GPSS)₁(AuNP/GPSS)₁₀) for methyl parathion (MP) sensing¹⁵³ (Fig. 7C). GPPDA was synthesized using graphene nanoplatelets stabilized in poly(diallyldimethylammonium chloride) (PDDA), and GPSS was synthesized using graphene nanoplatelets stabilized in poly(styrene sulfonate) sodium salt (PSS). SEM images showed that both (GPDDA/GPSS)₁₀ and (GPDDA/GPSS)₁(AuNP/GPSS)₁₀ films were wrinkled and undefined arrangement structures. Moreover, the distribution of AuNPs on the graphene sheet surfaces was random (Fig. 7D and E). On the basis of structural characterization, (GPDDA/GPSS)₁₀ and (GPDDA/GPSS)₁(AuNP/GPSS)₁₀ films interacted with MP through different adsorbing properties which were accounted for by the fact that the MP molecules can be distributed homogeneously on the film with AuNPs. Indium tin oxide (ITO) electrodes modified with the LbL films were applied by differential pulse voltammetry, achieving the detection of MP in real samples.

Fig. 7 (A) LbL fabrication process of MoS₂/Co₃O₄ nanocomposite film.¹⁵² (B) SEM images of Co₃O₄ (left), MoS₂ (middle), and MoS₂/Co₃O₄ (right).¹⁵² (C) Procedures to modify ITO electrodes with (GPPDA/GPSS)₁₀ and (GPDDA/GPSS)₁(AuNP/GPSS)₁₀ LbL films.¹⁵³ SEM images of LbL (GPDDA/GPSS)₁₀ (D) and (GPDDA/GPSS)₁(AuNP/GPSS)₁₀ (E).¹⁵³ Reproduced with permission from ref. 152 and 153. Copyright © 2017 and 2019 American Chemical Society.

For organic LbL systems, polyelectrolyte polymers are often deposited on flat substrates, where various materials can be also incorporated. A poly(3-aminobenzylamine)/PSS (PABA/PSS) multilayer thin film was developed, which was used as a electrochemical dopamine (DA) biosensor exhibiting a good sensitivity, linear range, low detection limit, long-term stability, and good reproducibility¹⁵⁴ (Fig. 8A). The PABA was firstly synthesized by chemical oxidation of 3-aminobenzylamine (ABA) monomer using ammonium persulfate (APS) as an oxidant. The morphologies of PABA powder and PABA/PSS thin films observed by SEM, as shown in Fig. 8B. PABA powder was not uniform in size and did not line up neatly on PSS, even displaying irregular stacking in multilayer PABA/PSS thin films. However, the PABA/PSS thin film deposited onto fluorine-doped tin oxide (FTO)-coated glass substrate enabled detection of DA. The construction of biodegradable LbL self-assembled drug delivery surfaces was investigated by Kim and co-workers.¹⁵⁵ The film was constructed based on the hydrogen bonding between poly(acrylic acid) (PAA) as a H-bond donor and biodegradable poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) micelles as a H-bond acceptor; this structure was assembled under acidic conditions (Fig. 8C). Due to the weak interactions of the hydrogen-bonded film on hydrophobic surfaces, flexible free-standing LbL thin film without an ordered structure can be generated (Fig. 8D) and can be allowed to disintegrate to release micelles upon exposure to physiological conditions. It was also demonstrated that such micelle LbL film loaded with antibacterial triclosan was fully functional in inhibiting the growth of Staphylococcus aureus (S. aureus). The micellar encapsulation of hydrophobic therapeutics does not require specific chemical interactions and takes up random positions, which can be used to control release properties.

Fig. 8 (A) Schematic diagram representing PABA/PSS LbL films assembled for the electrochemical detection of DA based on a biosensor on FTO substrate.¹⁵⁴ (B) SEM images of different number bilayer PABA/PSS thin films.¹⁵⁴ (C) Schematic representation of a hydrogen-bonding LbL assembly of block copolymer micelles for hydrophobic drug delivery carriers from surfaces.¹⁵⁵ (D) TEM micrograph of a cross-section of free-standing (PEO-bPCL/PAA)₆₀ film.¹⁵⁵ (E) Schematic of the formation and pH-triggered disassembly of polyelectrolyte LbL films composed of the polycations CH or CMCH and the polyanion TA.¹⁵⁹ (F) AFM images of (CH/TA)₂₀ and (CMCH/TA)₂₀ films.¹⁵⁹ (G) Schematics of 1 quad PDDA-SF-PDDA-Col LbL self-assembly formation on a glass slide surface.¹⁶¹ (H) SEM images of the surface of [PDDA-SF-PDDA-Col]_n film with different layers after LbL deposition.¹⁶¹ Reproduced with permission from ref. 154, 155, 159 and 161. Copyright © 2021, The authors; Copyright © 2008, American Chemical Society; Copyright © 2019 and 2019, Elsevier.

With increasing demand for being environmentally friendly, and for biodegradability, biocompatibility, and non-toxicity for nanomaterials, natural polymers (such as polysaccharides,^156,157 proteins, and poly-amino acids¹⁵⁸) are of great interest in LbL assembly research. Chitosan can react with other materials through interactions including electrostatic forces and hydrogen bonding, which allows fabrication of chitosan-based nanocomposites by LbL. For example, chitosan or N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (CMCH) and tannic acid (TA) were employed to form LbL assembly multilayer films with pH-responsive and antibacterial properties¹⁵⁹ (Fig. 8E). Both CH/TA and CMCH/TA LbL films with an irregular inner structure (Fig. 8F) exhibited a similar disassembly at pH 7.4 and showed antiadhesive activity against Escherichia coli (E. coli) and S. aureus. On the basis of N-grafted copolymers of chitosan with ether polyethylene glycol (PEG) or dextran (DEX) alternately deposited with dextran sulfate, LbL films with enhanced resistance to protein adsorption were obtained.¹⁶⁰ Natural proteins also can be used in LbL film to provide improved biological compatibility. An osseointegration surface for dental implant materials was manufactured with LbL self-assembly¹⁶¹ (Fig. 8G). The films were composed of silk fibroin (SF), collagen (Col), and PDDA, and films of PDDA-SF-PDDA-Col were constructed with a different number of layers: n = 0, 10, 20, 30, 40, and 50 through an immersion method. These coatings displayed molecular mobility on their surfaces, which enhanced biological properties, osteoblast cell proliferation, alkaline phosphate (ALP) activity, and total protein absorption. SEM images revealed that the surfaces of LbL films were not flat and had partial stripes (Fig. 8H). The examples mentioned above are based on organic materials assembled on flat surfaces without specific alignment sequences, but these films still have their functionalities in certain fields. It should be noted that structure and order in polymeric systems have been investigated,^162–164 but such order depends on self-assembly methods.

The aim of organic LbL films doped with inorganic components is typically to improve properties or to obtain additional functionalities in the resultant hybrid materials. Deng and co-workers designed a dual therapy implant coating on the 3D micro-/nanoporous sulfonated polyetheretherketone (SPEEK) via LbL self-assembly of Ag ions and Zn ions¹⁶⁵ (Fig. 9A). Three types of nutrient elements incorporating SPEEK coatings (Ag-SPEEK, Zn-SPEEK, and Ag/Zn-SPEEK) were prepared and characterized. SEM images indicated that SPEEK formed a 3D network structure with interconnected micro- and nanopores, and the size of the non-uniform micropores varied between 0.5 and 1.0 μm (Fig. 9B). The antibacterial assays demonstrated that the Ag-decorated and Ag/ZnO-co-incorporated SPEEK coatings effectively inhibit the reproduction of E. coli and S. aureus with a bactericide rate up to 99%. In addition, osteoblasts exhibited a higher level of ALP activity and osteogenesis-related genes on the Ag/ZnO dual-co-modified SPEEK coatings. Ag/Zn-SPEEK implant coatings have better antibacterial activity, biocompatibility, and the capability to hasten osteoblastic differentiation of the implant, which might be related to the ion-induced synergistic effect and the 3D porous topological structure. Chen and co-workers reported fabrication of Ag nanoparticles (AgNPs)/cellulose nanofibril (CNF) comprehensive thin films via LbL spray-coating¹⁶⁶ (Fig. 9C). Compared with AgNPs sprayed on SiO₂ substrates, the incorporation of CNF substrates resulted in a more uniform distribution of AgNP agglomerates and individual AgNPs through their network structure and absorption of partially dissolved AgNP clusters. However, AFM images have shown that the deposition of AgNPs onto CNF thin film was still not well proportioned (Fig. 9D). Nevertheless, the increase of hydrophilicity of the AgNP/CNF composite films and the localized surface plasmon resonance intensity of AgNP suggested their potential applications in antifouling coatings or label-free biosensors. Li and co-workers successfully prepared a hybrid coating consisting of hydroxyapatite (HA), AgNPs, and chitosan on a polydopamine (PDA)-modified titanium (Ti) substrate by the LbL assembly process¹⁶⁷ (Fig. 9E). PDA accelerated the formation of HA crystals and bridged the binding strength between HA and Ti substrate. The surface of substrate modified by polydopamine, and the hydroxyapatite crystals on the modified substrate both were not in order (Fig. 9F and G). It has been noted that the surface-deposited HA particles react with AgNO₃ to form silver phosphate nanoparticles (SP NPs) during the period of immersion in AgNO₃ solution. SP NPs with sizes ranging from 50 to 100 nm were partially agglomerated on the surface of HA to form small clusters (Fig. 9H). In this nanoarchitectonics system, chitosan nanofilm played an important role in controlling the release of Ag⁺ from the hybrid coating and effectively reducing the cytotoxicity of hybrid coating. The PDA/HA/Ag/CS coating exhibited a higher antimicrobial effect than HA and can damage the shape of bacterial cells (especially E. coli), and presented long-term osteogenesis.

Fig. 9 (A) Schematic drawing of the preparation of Ag/ZnO dual-decorated micro-/nanoporous SPEEK, and its bactericidal effect and osteogenic activity.¹⁶⁵ (B) SEM images of SPEEK, Ag-SPEEK, Zn-SPEEK, and Ag/Zn-SPEEK coating.¹⁶⁵ (C) Sketch of the layered structure of AgNPs on the SiO₂ substrate, AgNPs spray-coated onto a cellulose CNF thin film, and a AgNP/CNF mixture on the SiO₂ substrate, respectively.¹⁶⁶ (D) AFM images of the AS, AC, and AM samples with 10, 50, and 150 spray cycles, respectively.¹⁶⁶ (E) Schematic illustration of a hybrid coating on Ti implant via LbL method and its disruptive behavior on bacterial cell membrane.¹⁶⁷ (F) Electron microscopy images of polydopamine modification of the Ti substrate.¹⁶⁷ (G) TEM image of hydroxyapatite crystals on polydopamine-modified Ti.¹⁶⁷ (H) SEM image of Ag doped on the surface of HA.¹⁶⁷ Reproduced with permission from ref. 165, 166 and 167. Copyright © 2018, Wiley; Copyright © 2021, The authors, published by American Chemical Society; and Copyright © 2016, American Chemical Society.

3.2.2 LbL self-assembly on particles – 3D nanostructures for encapsulation. LbL self-assembly can also provide an excellent shielding effect for the encapsulated substrates or molecules and achieve the versatility of the resulting hybrid system through the selection and reasonable matching of materials constituting hierarchical films. Such multilayers are mainly formed by alternate deposition of polyvalent polymers, colloids, and biomolecules on particles which serve as sacrificial templates for making polyelectrolyte multilayer capsules. Electrostatic interactions, and the matrix used are more likely to comprise micro/nano inorganic particles. Herein, the multilayer structures obtained by LbL self-assembly on particles used as substrates, including those possessing asymmetric shapes, non-ordered arrangements of molecules, and local defects, are also discussed.

Originally, purely polymeric capsules were developed.^168,169 However, these hybrid systems with undesired structures still have an important value for research and application.¹⁷⁰ Inorganic nanoparticles have attracted extensive attention in biomedicine due to their good physicochemical properties, stimuli-responsiveness, and signal-enhancing capabilities, etc. However, their low dispersion stability caused by high surface polarity, surface energy, and nano-effects will greatly limit their applications, while the introduction of polymer coatings provides a feasible solution to this problem. In addition, particles with perfect or highly symmetrical structures are not easily available under natural synthetic conditions due to the principle of minimum energy, which makes it difficult to obtain hybrid particles with perfect structures.

In general, hybrid particles are composed of heterogeneously distributed polymers and inorganic nanoparticles with different properties. Due to the irregular structures or morphologies, the agglomeration effect of nanoparticles, the uneven coating thickness and hole defects caused by the random cross-linking mechanism of polymer chains in the liquid phase, the morphology and surface structure of the so-called hybrid particles cannot be precisely controlled, resulting in a sequence-imperfect structure, which can be observed from the microstructure of hybrid particles. Even so, these poorly structured complexes formed by LbL self-assembly still exhibited a good performance.

Polymers or even inorganic nanoparticles forming the layers of such capsules have been deposited in an aqueous solution on such sacrificial templates (or cores) as melamine formaldehyde (MF),¹⁷¹ SiO₂,¹⁷² titanium,¹⁷³ alumina,¹⁷⁴ CaCO₃,¹⁷⁵ carbon,^176,177 magnetic iron oxide,¹⁷⁸ and metal nanoparticles.¹⁷⁹ These particles are homogeneously dispersed in the polymer solution, and single or multiple layers are deposited by inducing the cross-linking between polymer chains and the mutual adsorption caused by the charge effect between the polymer and the surface of the nanoparticles. LbL technology is the most typical method to obtain a multifunctional composite coating. The formed hybrid particles integrate the excellent properties of the two materials, which endows them with high encapsulation efficiency and stimuli-responsive ability, giving them great potential for applications in the encapsulation, delivery and targeted release of drugs as well as in biosensors.^180,181 Furthermore, the resulting hybrid particles can be transformed into hollow capsules depending on the solubility of inorganic nanoparticles, such as CaCO₃ particles, which is completely soluble in acidic conditions.¹⁸² The versatility of the capsules results from several aspects, including that release kinetics can be controlled as the number of layers affects release kinetics.^183,184

Given that the spherical structure and porosity of vaterite endow it with relatively higher drug-loading efficiency, it can be defined as a good substrate for synthesizing LbL self-assembly system. Numerous combinations of polyelectrolyte layers with opposite surface charges have been applied to the surface of vaterite, such as dextran sulfate sodium salt/poly-L-arginine hydrochloride,¹⁸⁵ chitosan/hyaluronic,¹⁸⁶ sodium alginate/chitosan,¹⁸⁷ poly(allylamine hydrochloride) (PAH)/PSS,¹⁸⁸ poly-L-ornithine (PLO)/fucoidan,¹⁷⁵ mucin/protamine,¹⁸⁹ PDDA and PSS,¹⁹⁰ cationic-polycyclodextrin/alginate,¹⁹¹ and DA-modified alginate/titanium(IV) bis(ammonium lactato) dihydroxid,¹⁹² and phenylboronic compounds for glucose responsiveness.^193,194 Unlike the completely ordered molecular arrangement, although the LbL adsorption and non-covalent cross-linking of polymers lead to the formation of various imperfect surface structures, such as continuous and porous 3D network structures^186,188,191 or the concave-convex inner surface because of the penetration of the polymer into the pores,¹⁸² the resulting surfaces are denser and smoother than the original matrix,¹⁷⁵ and compared with porous CaCO₃ particles without multilayers, the hybrid carriers show higher loading efficiency and a synergistic release mechanism. Moreover, some multilayer capsules can maintain structural stability in physiological conditions or a reductive environment¹⁸⁶ (Fig. 10).

Fig. 10 Schematic illustration of an enzymatical disulfide-crosslinked hollow CS/HA microcapsules by LbL on the CaCO₃ sacrificial templates, the confocal laser scanning microscope (CLSM) images of FITC-dextran-loaded disulfide-crosslinked hollow chitosan/hyaluronic acid (CS/HA)₄ microcapsules incubated in PBS (pH 7.4) containing 5 mmol L⁻¹ dithiothreitol for 60 h at 37 °C (left bottom), and the SEM images of disulfide-crosslinked hollow (CS/HA)₄ microcapsule (middle) and disulfide-crosslinked CaCO₃@(CS/HA)₄ microspheres (right bottom).¹⁸⁶ Reproduced with permission from ref. 186. Copyright © 2018, American Chemical Society.

Mesoporous silica nanoparticle (MSN) is attractive as a stable carrier for biomolecules such as DNA, enzymes, proteins, etc., ultimately for drug delivery and biosensing due to facile preparation, controllable size, high surface area and biocompatibility. However, MSN usually requires surface modification to improve the comprehensive properties, and LbL self-assembly is one of the most favorable methods. Different polymer combinations can be adsorbed on the surface of MSN through the LbL technique. For example, HA/5,10,15,20-tetrakis(4-sulfonatophenyl)-porphyrin (TPPS4) can be alternately deposited on the particle surface by electrostatic adsorption to form a hybrid carrier, and the existence of the multilayer masks the mesoporous structure of SiO₂, which reduces the specific surface area, pore size, and pore volume of the original matrix, effectively hindering the leakage of drug molecules from pores.¹⁹⁵ Self-assembly structures are closely related to the properties of polymers, which in turn are affected by the charge distribution caused by such factors as the concentration of salt solution and pH.¹⁹⁶ In addition, polyamidoamine (PAMAM) dendrimers/chondroitin sulfate, Lys/HA/polyglycerol methacrylate (PGMA) have been studied as well,^197,198 and these polymer multilayers improve the stability of the hybrid system and the targeted release of drug molecules, despite the structural imperfections caused by the random cross-linking of the polymers.

Advanced sandwich-liked structures have been also developed. For example, Shi and co-workers first deposited oxidized alginate and protamine organic layers on the surface of CaCO₃ particles via the LbL technique and then prepared a SiO₂ template layer on the membrane by biomimetic silicidation, followed by biomimetic mineralization.¹⁹⁹ An organic–inorganic hybrid outer membrane was formed, and with the removal of CaCO₃ core and SiO₂ template, mitochondria-like multi-chambered microcapsules with microcavity dimensions and nanomembrane spatial structure were obtained (Fig. 11A). The microstructures of the intima and adventitia showed high densification but exhibited different thicknesses (intima: 70–140 nm; adventitia: 200 nm), and the structures of the inner and outer surfaces of the adventitia were asymmetric (Fig. 11B–E). Although the nanoparticles were not arranged in an orderly manner, which was unavoidable during the deposition process, this double-sandwich structure had better activity, selectivity, and recovery stability of loaded enzymes compared with single-chamber microcapsules. Also, the highly interconnected slit-like pores inside the microcapsules provided channels for the free diffusion of molecules, and the double-layer structure can hinder the leakage of molecules as well. In addition, the presence of intermembrane space molecules built up osmotic pressure and improved particle stability.

Fig. 11 (A) Scheme of the construction of multienzyme system through synergy of LbL self-assembly and biomimetic mineralization. High-resolution SEM (HRSEM) image of the inner membrane (B) and inner surface (D) of hybrid double membrane microcapsules. HRSEM images of the outer membrane (C) and outer surface (E) of hybrid double membrane microcapsules.¹⁹⁹ Reproduced with permission from ref. 199. Copyright © 2011, American Chemical Society.

Similar multilayers can be applied to mesoporous carbon particles with mono-dispersity to achieve surface modification and controlled drug release. For example, a hybrid carbon-based system was formed using polyethyleneimine (PEI) as the inner layer, followed by alternate deposition of PSS and PAH bilayers three times. In view of the surface asperity effect caused by the porous structure of carbon particles and the low charge in bare carbon, the first two PSS/PAH bilayers inevitably exhibited uneven thickness and local defects. Nonetheless, the presence of the polymer coating improved the biocompatibility and controllability of drug release of hybrid carriers, and provided room for the addition of specific receptors.²⁰⁰

Some metal salt particles are also considered as good candidates for matrix materials.²⁰¹ For example, hedgehog-shaped particles (HPs) prepared from Zn(NO₃)₂ replicating the tip geometry of pollen grains were coated with polymers and exhibited remarkable stability.²⁰² Indeed, in contrast to the easily agglomerated spherical or square particles with regular structure, the former particles with imperfect appearance showed high dispersion stability and were not affected by their hydrophobicity/hydrophilicity matches with the medium phase. To preserve this stability, the surface modification of the tip was designed with a high-density conformal coating consisting of polymers and AuNPs via the LbL technique. The combination of plasma activity, the dense buildup of NP, and the omnidispersible stability enabled HPs with multilayers to become more efficient surface-enhanced Raman scattering (SERS) probes for rapid multipath biosensing, since the sensitivity and reliability of SERS-based biosensing highly depend on the dispersion stability of particles.²⁰³ On the other hand, such HPs were shown to self-assemble into rod-like structures,²⁰⁴ which are scientifically interesting and practical from the application point of view, but imperfect structure-wise. Thus, in addition, those LbL-modified HPs offer unique capabilities for catalysts, aerosol drug carriers, and extraction processes, where dispersion stability in a wide range of polar media is critical, even though their structure is imperfect.

Notably, incorporating inorganic nanoparticles in the polymer film²⁰⁵ or spherical polyelectrolyte multilayer capsules brings additional functionalities. For example, the mechanical properties of capsules can be enhanced either by increasing the number of layers²⁰⁶ or incorporating inorganic nanoparticles²⁰⁷ as well as Raman signal peaks for easier detection and the antibacterial properties of the substrate material.^208–210 Metal nanoparticle coatings prepared on the surface of polymer substrates through LbL technology can impart metallic properties to the surface of polymers, thus giving the possibility of further processing (e.g. electroplating), which opens up a new avenue for decorative coating and surface metallization of polymer materials.²¹¹ It should be noted that the application range of microcapsules, particularly in biomedicine, is steadily growing.^170,212,213 Also, it can be added that polyelectrolyte multilayer capsules can be combined with polymeric films^214,215 to further extend the range of applications.

3.3 Hydrogels

Hydrogels are materials with mechanical properties situated between those of elastic solids and viscous liquids.²¹⁶ Hydrogels are hydrophilic gels with 3D network structures, which can be synthesized through different crosslinking methods using such polymers as natural polysaccharides, polypeptides, and derivatives. According to the nature of the cross-linking, hydrogels can be divided into chemical and physical types.⁴² The former is determined by covalent bonds, which have longer degradation times and stronger mechanical properties but may involve addition of cross-linking agents, which will affect the biological properties of the hydrogel.²¹⁷ The formation of physical hydrogels is driven by electrostatic interaction, hydrogen bonding, and chain entanglement, and is affected by physical factors such as temperature, pressure, pH, ionic strength, and the type of added phase. These effects can be interfered with or interrupted by environmental changes, resulting in imperfect sequence distribution and length of polymers. However, the formation process does not involve the adoption of potentially toxic cross-linking agents while keeping excellent performance, which increases the appeal of physical hydrogels. According to the formation principle, physical hydrogels can also be called self-assembled hydrogels, and represent a new class of architecture for biomedical applications.

3.3.1 2D nanostructures of hydrogels on substrates. In terms of the fabrication of hydrogel films, natural polymer-based hydrogel films are highly regarded due to their superior biocompatibility. Numerous accounts in the literature have reported that self-assembled natural hydrogel films were multifunctional for a various range of biomedical applications over the decades.^218–221 For instance, Cui and co-workers designed smart hydrogel actuators constructed from chitosan and sodium alginate for assessing biomedical applications.²²² The gradient chitosan/sodium alginate complex hydrogel film, which is nano-porous, ultra-strong, and has adjustable thickness, provides practical guidance for application in drug delivery, tissue engineering, soft robotics, and active implants. Acacia gum polysaccharide-based porous hydrogel films has been made by Singh and co-workers to explore antioxidant activity and improve its wound-healing potential.²²³

It is worth noting that an emerging approach to improve the physical–biochemical properties and the multifunctionality of biomaterials is the incorporation of functional hydrogels onto 2D surfaces. Surface-attached hydrogels are another tailored architecture comparable with polymer brushes and LbL assemblies as stable and durable polymer coatings which combine the advantages of both hydrogels and films.^224,225 A large range of inorganic substrates such as silicon wafers, glass substrates, and titanium surfaces can be chosen to introduce hydrogel films.^226–228 Lian and co-workers used a self-assembled peptide nanofibrous hydrogel composed of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) to construct a smart biointerface on the glassy carbon electrode.²²⁹ The interlaced nanofibers of Fmoc-FF hydrogel with some non-uniform pores acted as a matrix to embed an enzyme model for enzyme-based electrochemical biosensing, and was a robust substrate for cell adhesion to monitor H₂O₂ released from cells in situ. The polyimide-based thin film electrodes coated by a laminin-derived peptide can support neurons and reduce the risk of fibroblast-mediated fibrotic encapsulation.²³⁰ Notwithstanding the great potential of surface-attached hydrogel films, they are still rarely investigated except for very specific uses. This is probably due to the lack of a general strategy for the synthesis of reliable and reproducible self-assembled hydrogel films.²²⁶

3.3.2 3D nanostructures of hydrogels on particles. Polysaccharide-based self-assembled polyelectrolytes including cellulose,²³¹ HA,²³² CS,^217,233,234 alginic acid,²³⁵ pectin,²³⁶ gellan gum,²³⁷ alginate,²³⁸etc. (so-called physical hydrogels), can be prepared via electrostatic attraction of anions and cations without any chemical cross-linkers, and their final structures and properties are not only controlled by thermodynamics, but also related to the spatiotemporal sequence of cues that trigger self-assembly.²³⁵ Ultimately these hydrogels exhibit excellent biosafety, degradability, reversibility, and favorable drug-loading and release properties.²³⁹ These honeycomb or network-like frameworks composed of polymers usually possess a high porosity and interconnected pores which provide channels for drug diffusion, as well as cell adhesion and proliferation.^217,233,240 The distribution characteristics of these pores of hydrogel films are non-uniform and are accompanied by various pore sizes and a high local density packing. Local fractures also appear in the 3D framework, caused by the strength of the driving force.^217,233 Therefore, one can clearly find messy skeleton structures of the self-assembled hydrogels, rather than the regular structure similar to the football olefin or the Rubik's cube, although only changes in the morphology of hydrogels can be noticed from the macroscopically (Fig. 12).

Fig. 12 SEM images of the cross-sectional morphology of freeze-dried polysaccharides salecan hydrogel (A) and N,N,N-trimethyl chitosan hydrogel (B).²¹⁷ (C) and (D) SEM images of hydrogel formed by cellulose nanofibrils.²⁴⁰ Reproduced with permission from ref. 217 and 240. Copyright © 2019, Elsevier; and Copyright © 2018, Acta Materialia Inc., published by Elsevier.

Polypeptides have received extensive attention since they not only self-assemble into supramolecular structures, but they can also influence cell adhesion and differentiation by regulating their own biochemical and physicochemical properties. Notably, hydrogels formed by covalent cross-linking of polypeptides triggered by UV radiation, extreme pH, high temperature, or chemical agents such as glutaraldehyde often lack biocompatibility, which limits their applications in the fields of drug delivery vectors and tissue engineering. While such strong non-covalent interactions as hydrogen bonding, hydrophobic or electrostatic interactions provide feasible solutions for the preparation of transient, reversible polypeptide-based hydrogels, this may be at the expense of self-assembly, healing, stability, and flexibility, which can be compensated for by a reasonable combination of peptides.

In addition, anisotropic particles with complex, non-spherical, and asymmetric structures are favored because of their unique advantages, such as anisotropic responses to external forces, anisotropic building blocks for complex structures, which makes them attractive in applications for drug delivery systems, cell culture, and biosensing.²⁴¹ For example, Marquis and co-workers adapted dimethyl carbonate as continuous phase, or deforming pre-gelled droplets off-chip at a fluid–fluid interface to synthesize pectin hydrogel microparticles with ellipsoid, torus or mushroom-type morphologies. The connection between microfluidic diffusion-induced self-assembly and surface porosity was revealed by the microstructure of the surface of pectin hydrogel microparticles. In the case of internal gelation, the surface of the hydrogel was irregular and the pore size distribution of the microparticles surface ranged from 100 to 600 nm. Mushroom-shaped microparticles self-assembled to the undulating surface through a type of cap-to-tail binding in a topology-like manner and displayed rather loosely interconnected anisotropic “domains” (with a star-like structure) and local voids on the tail surface, which indicated that the gel crosslinking was not uniform, leading to the imperfect self-assembly structure²³⁶ (Fig. 13).

Fig. 13 SEM micrographs of the surface of pectin hydrogel microparticles.²³⁶ (A) Surface of pectin hydrogel microparticles when solvent diffusion applied; (B) surface of pectin hydrogel microparticles without solvent diffusion; (C) tail surface of the mushroom-like morphology microparticles; (D) cap surface of the mushroom-like morphology microparticles. Reproduced with permission from ref. 236. Copyright © 2014, Elsevier.

For example, combining positively charged poly-L-lysine with negatively charged Fmoc-FF enhanced the coordination and self-healing properties of the resulting hydrogels, which exhibited a dense network-like structure composed of long nanofibers.²⁴² Porous hydrogels with independently tunable biochemical, mechanical, and physicochemical performance parameters can be synthesized from self-assembled peptide amphiphile and PEG without any chemical modification or involvement of additional polymers. This hydrogel presented an opportunity for tissue engineering and regenerative medicine applications.²⁴³ Through the elimination of electrostatic repulsion of PBS, the polypeptide fibers and liposomes completed the gradual self-assembly, realizing the elongation, winding and gelation of the fibers, and the spherical liposomes were wrapped on the surface of the membrane structure by the fibers. Although not structurally appealing, this hybrid gel system combines the responsiveness of peptides to biological signals with the flexibility of loading and controlled release of liposomes.²⁴⁴

In addition, the microstructure and mechanical properties of self-assembled peptide hydrogels are closely related to cell proliferation, differentiation, and migration, which in turn can be determined by controlling the gelation speed through pH, ionic strength, and temperature. In general, higher ion concentrations can accelerate the hardening process of the gel, resulting in a more robust structure with smaller non-uniform mesh sizes, and extreme pH can cause this result as well.^245,246 Relatively milder conditions will result in the formation of more homogeneous, relatively soft hydrogels, although the microstructures are not completely ordered.²⁴⁵

Proteins are formed from one or more peptide chains, and the highly cooperative coordination of their subunits gives them enormous advantages for self-assembly.²⁴⁷ The amino acid residues are essentially weak electrolytes, which are distributed on the surface of the protein and endow the protein with different charge properties under different conditions, which provides the basis for the protein to complete self-assembly through electrostatic interactions.²⁴⁸ But these amino acids are usually unevenly distributed and form localized charge centers, which are related to the heterogeneity of the protein surface and ultimately cause imperfections in the protein structure. Although strong electrostatic attraction results in periodically ordered protein-based gels, weak interactions are generally not sufficient to induce self-assembly.²⁴⁷ However, a number of protein-based hydrogels have been synthesized from self-assembled protein fibrils and have been employed in numerous applications. Fibrinogen contains important binding sites to facilitate cell interaction and is able to form 3D hydrogels and nanofibrous fibrinogen scaffold.^249–253 For instance, Brüggemann's group introduced a simple and well-controllable bio-fabrication method to prepare nanofibrous fibrinogen hydrogel scaffolds by salt-induced self-assembly.²⁴⁹ Fibrinogen molecules change their conformation and are oriented during drying in the presence of salt ions. As the concentration of protein gradually increases upon drying, the oriented molecules aggregate into fibrils and induce fibrillogenesis²²⁰ (Fig. 14A). The structure of fibrinogen hydrogels induced by phosphate ions revealed a highly fascinating but not perfect porous fibrous network²⁵¹ (Fig. 14B). Fibrinogen hydrogels have great potential for wound-healing applications since they support fibroblast adhesion, prevent E. coli infiltration,²⁵⁰ and their multiscale structures can be well-regulated without inducing any pathogenic amyloid transitions.²⁵² Besides, amyloid fibrils also were investigated to form hydrogels which were triggered by various stimuli, such as heating/cooling,^254,255 changes in pH,²⁵⁶ or chemical additives.²⁵⁷ Das and co-workers developed a series of amyloid hydrogels based on the self-recognition motif of α-synuclein for promoting stem cell differentiation to neurons.²⁵⁴ Hu and co-workers found that amyloid fibrils can be driven into reversible hydrogels with antibacterial activity by adding natural polyphenols to amyloid fibrils present in the nematic phase²⁵⁷ (Fig. 14C). They also reported that flavonoid–amyloid fibril hybrid hydrogels inhibited the core molecular links between gut microbes and host intestinal lipid absorption for obesity control.²⁵⁸ Although the morphology of amyloid fibril hybrid hydrogels was homogeneously distributed in the AFM image (Fig. 14D), the arrangement of fibers was not orderly. Nonetheless, protein-based hydrogels still have great potential in the field of biomedicine.

Fig. 14 (A) Schematic illustration of fibrinogen assembles into fibrinogen hydrogel.²⁵¹ (B) SEM image of fibrinogen hydrogel treated with phosphate ions after 5 h.²⁵¹ (C) Schematic illustration of polyphenol-binding amyloid fibrils self-assembly into reversible hydrogels with antibacterial activity.²⁵⁷ (D) The AFM image of the morphology of the epigallocatechin gallate (EGCG)-induced amyloid fibril hydrogel.²⁵⁷ Reproduced with permission from ref. 251 and 257. Copyright © 2021, The authors, published by American Chemical Society; and Copyright © 2018, American Chemical Society.

DNA-based materials exhibit outstanding properties attributed to the supramolecular interactions among complementary base pairings of nucleic acids.²⁵⁹ Additionally DNA, as a strongly hydrophilic polyelectrolyte, is capable of absorbing large amounts of water, which sparks interest in DNA for hydrogel design.²⁶⁰ Among the most common chemical and physical techniques (including self-assembly, enzyme ligation, rolling circle amplification, and hybridization chain reaction) of synthesizing DNA-based hydrogels, self-assembly of Y-type DNA (three-way junction) by extended sticky ends was used to make the simplest form of DNA hydrogels.²⁵⁹ Xing and co-workers proposed a Y-shaped DNA and a double-stranded DNA as two kinds of building blocks to create pure DNA hydrogels with designable thermal and enzymatic responsive properties (Fig. 15A). The sticky ends of the Y-shaped DNA and double-stranded DNA as linkers are complementary to each other, and this hybridization may result in DNA-based hydrogel formation.²⁶¹ Ma and co-workers designed floxuridine-containing DNA and RNA as building units and further assembled into a nucleic acid-based spherical nanogel that exhibited excellent inhibitory activity against cancer cells.²⁶² As for single-stranded DNA (ssDNA), Hu and co-workers reported on the construction of pH-responsive DNA hydrogel based on the self-assembly of one short ssDNA (Fig. 15B). It was revealed that the self-assembly between the short ssDNA strands resulted in the formation of long linear DNA structures and looped structures, while the entanglement between these DNA assemblies at high concentrations led to the formation of 3D hydrogel networks.²⁶³ The microstructure of the freeze-dried DNA hydrogel was full of dense but irregular pores (Fig. 15C), confirming the existence of a cross-linked network structure of the system. DNA-based hydrogel as a novel kind of smart hydrogel with programmable functions, stimuli-responsiveness, excellent biocompatibility, and inherent biodegradability has high potential in biomedical applications.^263,264

Fig. 15 (A) Schematic illustration of DNA hydrogel formed from Y-shaped DNA. The DNA hydrogels exhibit thermal and enzymatic responsive properties.²⁶¹ (B) Schematic representation of the self-assembly of ssDNA (I-15) into a pH-responsive DNA hydrogel.²⁶³ (C) SEM image of the freeze-dried I-15 DNA hydrogel.²⁶³ Reproduced with permission from ref. 261 and 263. Copyright © 2011, Wiley; and Copyright © 2022, American Chemical Society.

Hybrid hydrogels with the incorporation of inorganic ions have attracted great attention in recent years for their excellent mechanical properties. Inorganic components including SiO₂,²⁶⁵ CaCO₃,²⁶⁶ Fe₃O₄ particles,²⁶⁷ graphene oxide,²⁶⁸ nanoclay,²⁶⁹ and carbon nanotubes²⁷⁰ have been introduced into organic hydrogels to expand their applications. For instance, Abalymov and co-workers designed a hybrid thermally annealed hydrogel with sodium alginate and CaCO₃, which has a porous and irregular particle arrangement morphology.²⁷¹ These hybrid hydrogels have tunable mechanical properties and were employed to control cell adhesion and proliferation.^271,272 Zhuang and co-workers demonstrated that an alginate/reduced graphene oxide double-network hybrid hydrogel exhibited a higher Young's modulus and a lower swelling ratio than the single-network hydrogel, which led to improved gel stability in highly concentrated alkali/salt solutions.²⁷³ Inorganic-doped hybrid hydrogels would be suitable representatives of toughened hydrogels because of the versatile functionalization of inorganic nanoparticles and their excellent mechanical strength and large specific surface area.^265,274

3.4 Other structures

A large variety of other structures exist in which perfect and imperfect self-assembly was used. These include assemblies composed using hydrophobic, magnetic and forces upon evaporation including such materials as quantum dots, nanocrystals, magnetic nanoparticles or magnetic nanoparticle-assisted assembly, and acoustic levitation. These structures are different from the assemblies described above, but they constitute an additional class of materials where perfect (high) and imperfect (order) is either used or is relevant for their functions. For instance, Co nanocrystals with low size distribution can self-assemble either in fcc colloidal crystals to form supracrystals or in films with voids.²⁷⁵ Au nanocubes, used as model building blocks, were used in acoustic levitation self-assembly.²⁷⁶

4. Applications

In this section, we mainly discuss different biomedical applications of polymer brushes, LbL self-assembly nanostructures, and hydrogels, which have been summarized in Table 2.

Table 2 Selected applications of polymer brushes, LbL assembly, hydrogels and other structures

	Materials	Type of structure	Functions	Applications	Ref.
Polymer brushes	Semiconducting polymer	3D	Light-responsive	Cancer therapy	351
			Specific release
			Inhibits tumor growth
			Deliver CRISPR/Cas9 cassettes	Gene therapy	349
			Control the endolysosomal escape
			Photothermal conversion
LbL assembly	Heparin + chitosan + polyurethane-coated decellularized scaffold	2D	Decreased hemolysis rate	Vascular tissue engineering	156
			Prolonged in vitro coagulation time
			Enhanced resistance to platelet adhesion
	β-Cyclodextrin-modified silk fibroin + adamantane-modified hyaluronic acid	2D	Self-healing	Nerve tissue engineering	375
			Antibacterial activity
			Enhanced cells proliferation
	Carbon nanotube + cellulose acetate nanofibers + chitosan	3D	Promote fibroblast attachment, spreading, and proliferation	Tissue engineering	301
	Chitosan + caseine + corona pretreated polylactic acid substrates	2D	Drug loading	Drug delivery	319
			Prolonged release
	Chitosan + dextran sulfate	3D	Drug loading	Anti-cancer drug delivery	376
			Controlled release
			Inhibition of HepG2 cells
	Silica nanoparticles + poly-L-ornithine + carboxymethyl lentinan	3D	High drug loading	Anti-cancer drug delivery	377
			Sustained release
			Anti-proliferative
	Indium tin oxide electrodes + polyallylamine hydrochloride + folic acid	2D	Detect cervical cancer cells	Cancer diagnosis	378
	Poly(lactide-coglycolide) + (poly L-ornithine/fucoidan)4	3D	Drug loading	Therapeutic	379
			Controlled release
			Anti-tumor activity
	Silica nanoparticle + per-O-methyl-β-cyclo-dextrin-grafted-hyaluronic acid + TPPS4	3D	Drug loading	Therapeutic and diagnosis	195
			Preferential accumulation in tumor site
			Inhibited the tumor progression
			NIR fluorescence/MR imaging
Hydrogels	Polyethylene glycol-based Fmoc-FF peptide hybrid polyurethane + curcumin	3D	Self-healing	Tissue engineering	380
			Suppressing the inflammation response
			Improve the cutaneous wound healing
	Helical N-acetyl-β^3-peptides	3D	Compatibility with neural cells	Neural tissue engineering	381
			Cells adhesion and proliferation
	Graphene oxide + nano-hydroxyapatite	3D	Enhance the proliferation, ALP activity and osteogenic gene expression	Bone tissue engineering	382
			Healed calvarial defects
	Coumarin-tris derivatives	3D	Stimuli responsive	Drug delivery	383
	Fmoc-FF peptide + alginate	3D	Sustained and controlled release	Drug delivery	341
	Alginate + carboxymethyl cellulose	3D	pH-Sensitive	Drug delivery	384
			Sustained release
	Alginate + silver nanoparticles	3D	Laser-induced	Drug delivery	363
			Enhance the Raman signal	Detector
	Alginate + silver nanoparticles + calcium carbonate	3D	Enhance the Raman signal	Drug delivery	362
				Detector
			Ultrasound-induced	Drug delivery	209
			Enhance the Raman signal	Detector
	Rhein	3D	Sustained release	Neuroinflammatory therapy	385
			Reversible stimuli-responses
			Bind to toll-like receptor 4
	DNA (unmethylated cytosine-phosphate-guanine oligonucleotides)	3D	Drug loading	Antitumor therapy	386
			pH-Responsive
			Controlled release
			Induced apoptosis of tumor cells
	Gold nanobipyramids conjugated silica nanoparticles + azobenzene and α-cyclodextrin-functionalized hyaluronic acid	3D	Sustained and selective drug delivery	Chemotherapy and photothermal theranostic platform	364
			Long-term drug release
			NIR and enzyme dual responsive
			Attach to tumor cells
Other structures	Semiconductor, metal and magnetic particles	2D or 3D	Sensors and biosensors	SERS	367 and 387
			Light responsive	Detectors

---

4.1 Tissue engineering

Tissue engineering is an interdisciplinary subject evolving from biomaterials and engineering development, and aims at the formation and regeneration of tissues or organs by assembling scaffolds, cells, and functional molecules into tissues.^290–292 To mimic the extracellular matrix of native tissues, the ideal scaffolds must meet some specific requirements, involving structural, physical, chemical, and biological properties and functions.^293,294 Taking into account the requirements, various multilayer nanofilms, nano-coatings, and 3D hierarchical structures have been designed for tissue engineering.

4.1.1 LbL self-assembly nanostructures. Multilayer nanofilms constructed by the principle of nanoarchitectonics can direct cellular phenotypes like cell adhesion, cell growth, and cell differentiation. For instance, Col and HA were deposited on the plasma membrane of live mesenchymal stem cells (MSCs) using the LbL assembly technique²⁹⁵ (Fig. 16A). Although Col/HA multilayer films did not entirely block the cell plasma membrane surface, instead of leaving a vast extent of the plasma membrane in a naked state, this structure displayed openness and flexibility. The multilayer Col/HA film significantly supported cell survival in the attachment-deprived culture condition even in its mesh-like form. Moreover, films induced cellular metabolic activity and upregulated osteogenic differentiation with no deteriorating effect or inhibition of cellular attachment. Nano-coatings acted as protective shells for cells and as a way to functionalize the cell surface by modulating the physiochemical properties of the coating such as thickness, components, and charge of multilayers. For example, a LbL multilayer assembly method was employed to coat the MSCs’ surface with hydroxyapatite (HAp) and Col for bone tissue engineering applications.²⁹⁶ The cellular reactions of MSCs including adhesion, proliferation, and osteogenic differentiation phenotype were examined by altering the surface contents of HAp and Col on the micro-structured scaffold. Encapsulation of cells has been demonstrated to effectively control cell functions through modulating the communication to the cellular environment, providing protection for cells against physical damage, or attenuating deleterious host responses. Shin and co-workers successfully created multilayered dense and tightly connected cardiac tissue by alternately depositing cardiomyocytes and PLL-coated graphene oxide (PLL-GO)²⁹⁷ (Fig. 16B). The architecture of the multilayer constructs improved cardiac cell organization, maturation, and cell–cell electrical coupling, and enhanced biological activity, mechanical integrity, ease of handling, and retrievability of engineered tissue. Single cells were also encapsulated into LbL-assembled fibronectin-gelatin (FN-G) nanofilms by Nishiguchi and co-workers.²⁹⁸ This cell accumulation technique by FN-G encapsulation of single-cell surface easily provided approximately 8L of 3D tissues after only one day of incubation, and the layer number, cell type, and location were all successfully controlled by changing the number and order of seeded cell.

Fig. 16 (A) Schematic illustration of the Col/HA LbL film on MSCs. Col and HA can bind with integrin and CD44, respectively, forming a stable multilayer on the MSC. The multilayer Col/HA films increased cell survival in the attachment-deprived culture condition.²⁹⁵ (B) Schematics displaying electric signal propagation through hybrid hydrogels in cardiac tissue engineering.²⁹⁷ (C) Illustration of the adaptive biointerface with dual responsiveness for tissue engineering. A cell-adhesive peptide layer, an infectious-environment-responsive peptide, and antifouling HEG layers were included in the self-assembled peptide surface. The adaptive capability of this biointerface was realized with a smart responsiveness toward healthy and infectious tissues.³¹⁰ Reproduced with permission from ref. 295, 297 and 310. Copyright © 2017 and 2019, American Chemical Society; and Copyright © 2015, Wiley.

Compared with single inorganic or organic particles, hybrid systems based on LbL self-assembled polyelectrolytes, especially the multilayer polymer coating of inorganic or organic particles, have a relatively suitable structure with rough surfaces and reasonably tunable mechanical properties determined by the cross-linking mechanism of the polymers and the characteristics of the LbL self-assembly technique, which will facilitate cell adhesion, migration, proliferation, and allow filling of tissue defects. For example, the biomedical applications of polyester materials are restricted due to their hydrophobicity and weak bioactivity. The lack of appropriate cell-binding signals leaves them undesirable for cell adhesion and proliferation.²⁹⁹ It has been documented that modification of the scaffold surfaces with natural macromolecules by LbL self-assembly is a promising approach to mimic the organic component of nature and improve the biological properties of the substrates. He and co-workers constructed laminin/chitosan multilayers on poly-L-lactic acid (PLLA) nanofibers to provide a better environment for neuron growth and neurite outgrowth. Higher amounts of laminin embedded in the architecture and maintained a secondary structure close to their native form that better assisted in promoting cell proliferation than PLLA nanofibers.³⁰⁰ However, most research has focused on multilayer coating on nanofibers^301,302 or metal alloys,^303,304 and the functionalities of LbL coating on particles for tissue engineering need to be further conducted.

4.1.2 Hydrogels. Self-assembled hydrogels with interconnected porous structures can provide channels for cell growth and migration, and the rough surface supports cell adhesion, growth, and differentiation as well.^305–307 Such hydrogels have important applications as 3D scaffolds for tissue engineering. For example, unmodified chitosan hydrogel-encapsulated mesenchymal stem cells and chondrocytes can effectively support the proliferation and deposition of extra chondral matrix, and the addition of native type II collagen and chondroitin sulfate increases cell cohesion and cartilage-like cluster formation, and further promotes the regeneration of cartilage.³⁰⁸ The chitosan/polyglutamic acid hydrogel formed without the participation of any toxic cross-linking agent shows good shape-retaining ability, and the interconnected porous and rough surface structure are ideal for cell adhesion. It creates a favorable biological environment for tissue growth and proliferation, and also provides efficient channels for tissue growth and nutrient exchange, ultimately effectively inducing the growth of osteoblasts. The percentage of new bone formation after six weeks of hybrid system containing calcium sulfate dihydrate was as high as 70%.³⁰⁵ Self-assembled peptide-based hydrogels with 3D network structures which are similar to polysaccharide-based hydrogels have been explored for use as 3D tissue engineering scaffolds as well, due to their good biocompatibility, immunogenicity, degradability, and non-toxic byproducts, and have been extensively reviewed.^{221,309–311} The self-assembled peptide can be assembled as a dual-responsive bio-interface for infection prevention and tissue self-healing³¹⁰ (Fig. 16C). These peptides can be induced to self-assemble to form hydrogels through changes in pH and ionic concentration, and hydrogels with a reasonable strength and enhanced specific tissue priorities (e.g., osteogenic differentiation, drug delivery, or tunable gelation) can be obtained through modulation of peptide sequence and peptide concentration.^312–314 They can be easily injected and can be used as bone-filling materials, and their inherent network structure with relatively rough surface is conducive to cell adhesion, proliferation, migration, and differentiation.³¹⁵ For example, the hydrogels comprising β-sheet-forming peptides rich in aspartic amino acids and of tricalcium phosphate (β-TCP)-loaded hydrogels can significantly induce osteoblasts in vitro, and in vivo studies on bone defect healing in rat distal femurs analyzed by micro-computerized tomography showed that the peptide hydrogel itself induced better bone regeneration in comparison with non-treated defects.³¹⁶

4.2 Drug delivery

The development of smart drug-delivery systems for controlled drug-loading and manner of release has been an active area of research.^317,318 Many aspects are essential when considering the design of novel drug-delivery platforms, including drug dosage, loading efficacy, controllable release, side effects, and toxicity. Hierarchical self-assembled systems offer impressive advantages of tailorability and versatility, which are crucial for controlled and targeted drug release.

4.2.1 LbL self-assembly of nanostructures. Multilayer polysaccharide-based films are capable of high drug loadings due to their stable and porous structures. For example, the LbL deposition technique was applied for the build of multilayers which were performed by alternate dip-coating of corona pretreated polylactic acid substrates into chitosan and casein solutions.³¹⁹ The cross-linking process of chitosan and casein resulted in stable and porous film structures, leading to the highest benzydamine loading of 217.4 μg cm⁻². Drug-loading efficacy can also be readily tuned by changing the number of layers. Albright and co-workers have demonstrated that the antibacterial efficacy of antimicrobial-hosting coatings was enhanced by a simple increase of the number of assembled polymer layers.³²⁰ Multilayer films have abilities to protect drug molecules from harsh environmental factors which can cause the loss of therapeutic effects, and control the drug release rate by the rate of diffusion or by the rate of their dissolution or degradation. For instance, Redolfi Riva and co-workers reported a free-standing polymeric ultrathin film, composed of poly(methylmethacrylate) (PMMA), chitosan, and sodium alginate multilayers, which was loaded with anti-inflammatory drugs.³²¹ The structural layer of PMMA augmented the mechanical performance of the films and hindered the dispersion of drugs by acting as a barrier for the directional release. Drug-release modeling with the Korsemeyer–Peppas model illustrated that drug release was characterized by a diffusion-controlled mechanism. Mohanta and co-workers fabricated LbL-assembled multilayer thin films and hollow microcapsules employing nano-crystalline cellulose (NCC) and chitosan as a carrier for drug delivery³²² (Fig. 17A). The films have porous nanofibrous morphology and can be loaded with a substantial amount of the hydrophilic drug doxorubicin (Dox). The films also showed favorable interaction of NCC with the water-insoluble drug curcumin via hydrogen bonding and van der Waals interactions, in molecular docking studies. Both Dox and curcumin were released continuously in physiological conditions simulated by PBS buffer of pH 7.4. The sustained release manner of this film drug-delivery system prolongs the availability of drugs at the site of action. Hybrid inorganic–organic films fulfill great potential for antimicrobial drug delivery due to the synergetic effects of polymer with inorganic materials. Türk and co-workers developed an innovative LbL coated titanium hydroxide-(gentamicin-polydopamine) hybrid drug delivery platform³²³ (Fig. 17B). The multilayer coatings containing gentamicin demonstrated an improved drug-release time and in vitro inhibitory effect on the growth of S. aureus.

Fig. 17 (A) Schematic representation of multilayer thin films and hollow microcapsules as a carrier for Dox and curcumin delivery.³²² (B) Schematic illustration of fabrication processes of non-simultaneous titanium hydroxide-gentamicin-polydopamine ((TiOH-Gent)-PDA) and simultaneous TiOH-(Gent-PDA) LbL hybrid coatings. The multilayer hybrid drug delivery platforms demonstrated an inhibitory effect on the growth of the S. aureus.³²³ (C) Schematic representation showing the outline of the LbL MPs design and the effect of the MPs in the tumor environment.¹⁷⁵ (D) Schematic illustration of light-responsive Fe³⁺-polysaccharide coordination hydrogels for controlled drug delivery.³³⁹ Reproduced with permission from ref. 322, 323, 175, and 339. Copyright © 2014, American Chemical Society; Copyright © 2021, Elsevier; Copyright © 2018, Springer; Copyright © 2015, American Chemical Society.

The LbL self-assembly systems based on particles have a high loading efficiency which is provided by the porosity of carriers. The trapping effect of the network structure will hinder the short-term and rapid release of drugs, and finally form a good drug sustained-release system. For example, the hybrid drug-delivery system formed by CaCO₃ particles combined with various polyelectrolyte coatings has higher stability and longer-lasting drug-release efficiency than single nanocarriers without coating¹⁷⁵ (Fig. 17C). Because the polyelectrolyte multilayer can stably exist in an acidic environment and undergo network shrinkage, the drug-burst effect caused by the easy degradability of CaCO₃ in an acidic environment is alleviated.^324,325 In addition, the multifunctional groups on the surface of the polyelectrolyte multilayer make surface modification easier, which is more efficient for cellular uptake and the targeted induction of hybrid carriers.^158,326 Importantly, the preferential ionization of the outer layer will change the permeability of the multilayer in the medium with different environments and time, and finally shows different responsive release behaviors. For example, Elbaz et al. adopted poly-L-arginine/alginate to preferentially prepare two bilayers, followed by poly-L-arginine/Eudragit L100 and/chitosan/Eudragit L100 as the fifth and sixth layers, respectively. The former has no pH responsiveness, showing a delayed release effect in an acidic environment, but a rapid release in the intestinal environment; the latter shows pH responsiveness, which can effectively protect the drug in the gastric acid environment, and also plays an important role in limiting drug release in the intestinal environment, which is of great value for colon-targeted drug delivery.³²⁷ Also, the composite multilayer can provide a diversity of encapsulated drugs and provide the combination therapy of segmented release.³²⁸ Moreover, the addition of multifunctional nanoparticles before the self-assembly of polyelectrolyte multilayers will also confer stimuli-responsiveness to the hybrid carrier.^329,330 Some polyelectrolyte multilayers have pH-dependent ionization degree, near-infrared light, and thermal sensitivity, and the resulting polymers show good pH, light, and thermal responsiveness, which provides a basis for targeted drug release.^331–333

4.2.2 Hydrogels. As mentioned above, self-assembled hydrogels have reliable biocompatibility compared with the hydrogels formed by chemical cross-linking and possess the general properties inherent in hydrogels, including high water content and network-like structure. It should be noted that this type of hydrogel has good self-healing properties and strength, which gives them great potential in drug delivery systems.³³⁴ For example, a 3D network-like self-assembled hydrogel system composed of anionic TEMPO-oxidized cellulose nanofibers and cationic guar gum through electrostatic/hydrogen bonding has good self-healing and strength, showing a good sustained-release effect in gastrointestinal conditions, since the nano-locking effect produced by the network structure delays the release of the drug.³³⁵ This is also reflected in the double-membrane hydrogel drug delivery system formed by cationic cellulose and sodium alginate.³³⁶ Injectable hydrogels prepared from ethylene glycol and chitosan have good stability and coordinated heat sensitivity, and are considered to be a good alternative material for the treatment of intervertebral disc herniation.³³⁷ Polysaccharide hydrogels formed with HA and CS effectively achieved the side effects of MMP inhibitors.³³⁸ The self-assembled hydrogels formed from alginic acid and pectin have good light responsiveness, which provides effective guidance for the controlled release of drugs³³⁹ (Fig. 17D). Ding and co-workers constructed a degradable, reversible hydrogel using dual physical dynamic bonding of host–guest chemistry and electrostatic interactions. This delivery vehicle exhibits a good biocompatibility and controlled release of growth factors in applications such as wound healing and ischemic tissue repair.³⁴⁰ A polysaccharide–peptide hybrid hydrogel formed by calcium ion-triggered co-assembly of Fmoc-FF peptide and alginate has better performance than alginate hydrogel or Fmoc-FF hydrogel. The high stability may be due to the synergistic effect of non-covalent and ionic interactions, and the hybrid hydrogel microspheres have a dense surface structure and a porous nanofiber network inside, which exhibit a well-controlled release effect on docetaxel. The release index n indicates that docetaxel is released from the hybrid beads mainly in a Fickian diffusion-mediated manner.³⁴¹ The controlled release of drugs from self-assembled peptide hydrogels can be achieved by adjusting the mechanical strength and porosity determined by the self-assembly conditions, combined with pH value and properties of drug molecules.³⁴² In addition, the mechanical responsiveness, self-healing, and thixotropy of peptide hydrogels are crucial for injectable drug loading systems, which enable smooth drug delivery without destroying the carrier and blocking pinholes.³⁴³ Also, the self-assembled peptide sequence can be effectively combined with some growth factors, hormones, and protein drugs to form a non-toxic and biodegradable hybrid drug-loading system, so as to successfully deliver drugs to myocardial tissue.^344,345

4.3 Theranostics

Nano-carriers can be exploited alone for therapeutic purposes or for a combination of therapeutic and diagnostic objectives. In such a combined application, the nanoplatforms can deliver both imaging and therapeutic agents for precision medicine.^346,347 Nanoarchitectonics research has focused on the fabrication of various nanostructures that have the capability to be used for cancer diagnosis and treatment.³⁴⁸ These delivery carriers are useful for theranostics, particularly as multicompartment carriers, which can be envisioned to encapsulate sensor molecules in some compartments and medically relevant molecules in other compartments. Owing to their unique physical and optical properties, the functionalities of therapeutics and imaging diagnosis can be achieved.

4.3.1 Polymer brushes. Semiconducting polymer brushes (SPBs) are employed as advanced photonic theranostic nanostructures with good biocompatibility, stable photophysical properties, and sensitive and tunable optical responses from ultraviolet to near-infrared (NIR) II window.³⁴⁹ SPB with a typical amphiphilic structure is convenient for forming semiconducting polymer particles (SPNs) in solvent via self-assembly, which can improve the optical-electronic and nano-structural properties.^295,350 For example, Cui and co-workers reported that the SPBs structure grafted with chemo-drug side chains through hypoxia-cleavable linkers can be directly self-assembled for cancer photoactivated chemotherapy treatment.³⁵¹ After systemic administration of semi-conducting polymer nanoprodrug (SPNpd) into the tumor-bearing living mice through tail vein, the NIR fluorescence images were longitudinally acquired to observe the biodistribution and accumulation of SPNpd at the tumor site. The mouse tumor growth was significantly inhibited because of the release of bromoisophosphoramide mustard intermediate and killing of cancer cells by inducing their DNA crosslinking. Li and co-workers designed an amphiphilic SPB that can self-assemble in water to encapsulate dexamethasone (Dex) for the remote control of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing³⁴⁹ (Fig. 18A). A tumor model was used to demonstrate that SPNs can accumulate in the tumor and showed accelerated Dex release and gene endolysosomal escape after laser irradiation. Subsequently, the payload release of CRISPR/Cas9 cassettes allowed highly efficient genome editing. The unique feature of SPBs-based NIR-II emission was useful for tracking and guiding genome editing in vivo, which increased the accuracy of the genome editing manipulation.

Fig. 18 (A) Design of SPB-Dex nanoparticles for CRISPR/Cas9 delivery, and illustration of the intracellular genome editing process upon 808 nm laser irradiation.³⁴⁹ (B) Schematic representation of the construction of functionalized LbL self-assembled polymeric film, and the study of spheroid adhesion.³⁵² (C) Schematic diagram of hybrid LbL-AuNP coatings around cells. By exposing LbL-coated cells with gold nanoparticle aggregates to a 785 nm laser, a strong localized heating can be induced resulting in necrotic cell swelling.³⁵³ (D) Schematic representation of the targeted drug delivery to tumor tissue based on Dox-loaded, polymer (azobenzene and α-cyclodextrin functionalized hyaluronic acid), and gold nanobipyramids conjugated mesoporous silica nanoparticles/hydrogel switchable system.³⁶⁴ Reproduced with permission from ref. 349, 352, 353 and 364. Copyright © 2019, Wiley; Copyright © 2020, Elsevier; Copyright © 2021, The authors, published by Elsevier; and Copyright © 2016, American Chemical Society.

4.3.2 LbL self-assembly nanostructures. LbL self-assembled multilayer architectures are also highlighted in theranostics research because of their ease of design and the potential to achieve a variety of stimulus responses, such as pH, temperature, and light responsiveness. Janardhanam and co-workers prepared pH-sensitive functionalized LbL self-assembled polymeric film composed of chitosan and sodium alginate loaded with 5-Fluorouracil (5FU) as the model chemotherapeutic agent against colorectal cancer³⁵² (Fig. 18B). Studies in a non-everted rat colon-sac model and open colon membrane model showed great permeation of 5FU across the colon wall when adhered to the chitosan side of LbL film. Cell monolayer and 3D-spheroid model studies indicated significant growth inhibition of cancer cells by 5FU-loaded film compared with free 5FU solution. Furthermore, a versatile theranostics nanoplatform can be archived by LbL self-assembly of metal particles and organic polymers. The unique photothermal conversion properties of metal nanoparticles suggested that they can perform as a phototherapeutic for cancer therapy. Our group proposed a new strategy of cancer fibrosarcoma MCA205 cells encapsulation in a hybrid coating containing LbL assembly polyelectrolytes functionalized with AuNPs aggregates³⁵³ (Fig. 18C). Upon exposure to laser illumination operating in a biologically “friendly” near-infrared spectral window, AuNPs aggregates can absorb the laser beam and convert it into heat, resulting in localized heat that caused immediate necrosis of the encapsulated cancer cells. Besides, functional inorganic nanoparticles such as silica nanoparticles can also be coated with polymers using the LbL technique, endowing them with additional characteristics, such as magnetic functions, electrochemical properties, and radioactivity, for various therapy and diagnostic applications. Mesoporous silica nanoparticles loading tirapazamine with LbL-assembled multilayer can be further constructed as an excellent photosensitive theranostic nanoplatform via host–guest interaction and the chelation with paramagnetic Gd³⁺. The nanoarchitectonics can be specifically taken up by CD44 receptor overexpressed tumor cells and respond to hyaluronidase to trigger the release of therapeutics, which exhibited a preference for accumulation at the tumor site and significantly inhibited the tumor progression. The in vivo tumor-targeting ability the nanoarchitectonics was investigated using NIR fluorescence and MR imaging.¹⁹⁵ LbL organic nanoparticles for effective cancer photoimmunotherapy were realized through the combination of NIR therapy and regulatory T-cell modulation.³⁵⁴ LbL self-assembled poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles coated with poly-L-histidine (PLH) and poly(ethylene glycol)-block-poly(L-glutamic acid) (PEG-b-PLG) with stimulus-responsive behavior, longer blood circulation, and better biocompatibility, can be successfully targeted to the Treg cells within the tumor microenvironment to abrogate their immunosuppressive function, which was expected to improve tumor ablation efficacy.³⁵⁴ Diagnostic functionality of LbL self-assembly nanostructures can include pH sensing,³⁵⁵ photothermal sensing,³⁵⁶ other ion-sensing capabilities³⁵⁷ or even mechanical sensing,^203,358 which can also initiate the release.³⁵⁹

4.3.3 Hydrogels. Self-assembled hydrogels have been employed to provide well-controlled drug release and targeted therapy in theranostics, affording greater patient comfort and efficient therapy. Injectable hydrogels have the potential for non-invasive administration, and can be delivered together with the aqueous pre-gel materials via syringe injection, and trapped at the target sites.³⁶⁰ Polymer-based hydrogels contain both natural and synthetic polymers with biocompatibility and robust structures, as well as a range of physiochemical and mechanical properties that can meet various requirements in vivo. Some inorganic materials such as metallic nanoparticles,^{209,361–363} silica,^364,365 and carbon materials³⁶⁶ can be incorporated into hydrogel networks to render them multifunctional. Various applications have been developed using this type of structure, in which either electrostatic, hydrogen bonding or hydrophobic, steric, or magnetic forces have been used. A notable application is SERS, which enhances a weak Raman scattering signal.³⁶⁷ For example, in situ functionalization of the hydrogel capsules with silver nanoparticles can provide multiple functionalities: make the capsule's shell a sensor platform to enhance the Raman signal and as result detect the molecule; be an important structural element of the shell and enhance the mechanical property; and provide a sensitivity to the laser³⁶³ and ultrasound irradiation,²⁰⁹ which enable a remote release of the payload after administration.³⁶³ Chen and co-workers reported an injectable drug delivery system for sustained cancer treatment using polymer (azobenzene and α-cyclodextrin-functionalized hyaluronic acid) and gold nanobipyramids-conjugated mesoporous silica nanoparticles³⁶⁴ (Fig. 18D). The light-induced platform has the specific affinity to the CD44 antigen overexpressed on tumor cells, and in situ self-assembled into a hydrogel under NIR radiation. Due to the upregulation of hyaluronidase (HAase) around the tumor tissue, further degradation of the HA in the hydrogel will result in the release of drug from the hydrogel, which can then be taken up by tumor cells and delivered to the cell nuclei. The intrinsic characteristics of polysaccharides, especially their enzymatic degradation and non-immunogenicity, make them the preferred choice for hydrogel preparation for theranostics. Chitosan-based hydrogel can facilitate lysosomal degradation and does not induce immune responses, and has been employed as drug delivery carrier for cancer treatment.³⁶⁸ The initial burst release effect of the chitosan-based hydrogel can be inhibited by an alginate surface layer, which improved the sustained-release behavior and radiolabeling stability of the formulation.³⁶⁹ Notably, most cancers are associated with the abnormal activities of phosphatases and/or kinases. Peptide-based hydrogel can be used as a biocompatible molecular probe for detecting the activity of phosphatases and kinases, which is a simple and easy method for quick measurement. For example, Yang and co-workers designed a self-assembly/disassembly system of supramolecular hydrogel based on a phosphatase/kinase switch to examine the activities of phosphatase and kinases.³⁷⁰ The hydrogel turned into a gel-sol phase transition in the presence of adenosine triphosphates and kinase, then phosphatase was added to the resulting solution that transformed it back to the hydrogel.

Successful in vivo transformation indicated that this biomimetic approach for regulating the state of supramolecular hydrogel could be a promising way to detect the activities of phosphatases and kinases. Peptide-based hydrogel also acts as a carrier to deliver drugs to tumor sites, enhances drug stability, improves the optical properties of photosensitizers, and increases the immune response.^371–373 A novel peptide-based self-assembled hybrid hydrogel with a high antitumor efficacy enabled photoacoustic and fluorescence imaging as demonstrated by Jin and co-workers, which served as a multifunctional vehicle for the delivery of drugs to tumor sites for cancer photothermal therapy.³⁷⁴

5. Conclusion and perspective

In this review, we describe recent research activity focusing on nanoarchitectonics. It is emphasized that architectonics at the nano-level, nanoarchitectonics, is different from that at macro- and micro-architectonics as well as atomic arrangements, particularly in crystals. Within the area of nanoarchitectonics, two sub-areas are described: self-assembly where order can be achieved and assembly with non-perfect order. Having provided a brief overview of the former, the focus of this review is on the latter area, where polymer brushes, LbL, and hydrogels are described. LB technology and lipids self-assembly are precise for constructing well-structured nano-units and have been summarized in many previous works. Conversely, nanostructures without perfect order and alignment have been classified as those based on 2D nanostructures (for example, for surface modification) and 3D nanostructures (for example, for encapsulation and drug delivery). According to different types of self-assembly, the principles of preparation are discussed, and the imperfect cross-linking structures are mentioned, and their biomedical applications are discussed as well. Polymer brushes, LbL nanostructure, hydrogels, and other structures are listed, revealing that each nanoarchitectonics assembly has its own characteristics and functionalities. (1) Polymer brush is one of the simplest strategies for functionalizing material surfaces, exhibiting fascinating physicochemical properties and versatile architectures. As a unique class of functional materials, polymer brushes combine the functionalities of matrix and the properties of tethered polymers, the self-assembly of polymers under solution can improve the nano-structural properties, including stimulus-responsiveness, superhydrophobicity, antifouling, and so forth. Therefore, they show great potential in theranostics by taking advantage of their structure and synergetic properties. (2) LbL assembly is an effective way for preparation of controlled nanoarchitectonics structures; both LbL assembly on organic/inorganic surfaces and particles are versatile and useful for a wide range of biomedical applications. Multilayer films constructed on flat surfaces using LbL assembly are advantageous for device structures and the preparation of biocompatible layered nanoarchitectures. The design of inorganic, organic, and hybrid LbL films is useful for development of ideas, protocols, and developments between these different research communities. LbL self-assembly structure on particles makes the physiochemical properties of particles complementary to that of polymers. High surface area may facilitate the increase of drug-loading concentration or even the spatial control of drug presentation. (3) Hydrogels are solid-like materials with large amounts of water, and are similar to the native extracellular matrix and possess the great ability to capture bioactive molecules. Natural supramolecular self-assembled hydrogels can improve cellular permeability and regulate the biological action of other pharmaceutical agents. The incorporation of particles in the matrix of hydrogel is a feasible approach to improve the strength of the hydrogel and reinforce the weak hydrogel network. Hybrid hydrogel provides multiple functions including sensitivity to several stimuli and programmable response. Even in nature not everything is perfectly ordered, like crystalline liquid, and tree skeleton made of cellulose; however, these structures still play quite a unique role there.

As mentioned above, although significant advances have been achieved with self-assembled hierarchical nanostructures, several challenges remain for their future developments. We believe that nanoarchitectonics is not a simple extension of what is observed in nanometer regions, and it is an amalgamation of many disciplines (such as supramolecular chemistry, materials fabrications, and biotechnology) and technologies (including microtechnology and nanotechnology). Nanoarchitectonics has two core missions for true development in nanoscience and related engineering outputs: (1) materials are architected through controlled and coordinated interactions to create unexpected functions, and (2) controlling nano-functions by simple macroscopic mechanical actions to utilize cutting-edge frontier science in daily life.³⁸⁸ However, the production of nano-sized objects has many uncertainty factors including thermal fluctuations, quantum effects, and statistical distributions, which may result in nano-specific phenomena that are unexpected or not easily controllable. Besides, most nano-sized objects have simple structures, which offer a limited level of nano-sized control. Other challenges are the selection of molecules and ‘decision-making’ based on the harmonization of multiple and sometimes ambiguous responses. Nanoarchitectonics based on self-assembly relies on both exploration of chemical designs³⁸⁹ and self-assembly processes.³⁹⁰ Self-assembly can be found in biomolecular evolutionary processes, which can be mimicked in artificial systems. In-depth studies of self-assembly processes of biological systems will help in establishing highly sophisticated functional nanoarchitectonics that have not been fully realized in artificial self-assembly. Moreover, by mixing two simple amphiphilic liquids,³⁹¹ the self-assembly processes can bring a dramatic variation of materials even without creating entirely new molecules, and chemical modification can open up molecular engineering strategies to biology,^29,392,393 and these procedures will provide improved building blocks for nanoarchitectonics for developing yet more applications, including nanomedicine.³⁹⁴

As discussed here, situated between micro- and atomic levels or sub-nano architectonics where fabricated objects typically follow the conceptual design, nanoarchitectonics produces structures which do not often follow the projected design due to the influence of molecular interactions. And in this area, the imperfect self-assembly methods discussed in this review provide a wealth of knowledge and enable a myriad of applications at this important nanoscale size range. All these factors make this area both interesting and challenging, underlining Richard Feynman's famous saying: “there is plenty of room at the bottom”, even if the bottom here is not at the lowest (atomic) size-scale level and even if it does not have a perfect (high) order assembly.

Abbreviations

STM	Scanning tunneling microscopy
TEM	Transmission electron microscopy
SEM	Scattering electron microscopy
AFM	Atomic force microscopy
CLSM	Confocal laser scanning microscope
LbL	Layer-by-layer
LB	Langmuir–Blodgett
3D	Three-dimensional
2D	Two-dimensional
PSCs	Polymer single crystals
P(SBMA-co-DMAEMA)	Poly[(sulfobetaine methacrylate)-co-(2-(dimethylamino) ethyl methacrylate)]
PDMA	Poly(dopamine methacrylamide)
MPBs	Molecular polymer brushes
PS	Polystyrene
PLA	Polylactide
QDs	Quantum dots
AuNPs	Au nanoparticles
MoS2	Molybdenum disulfide
Co3O4	Tricobalt tetraoxide
MP	Methyl parathion
PDDA	Poly(diallyldimethylammonium chloride)
PSS	Poly(styrene sulfonate) sodium salt
PABA	Poly(3-aminobenzylamine)
DA	Dopamine
ABA	3-Aminobenzylamine
APS	Ammonium persulfate
PAA	Poly(acrylic acid)
PEO-b-PCL	Poly(ethylene oxide)-block-poly(ε-caprolactone)
S. aureus	Staphylococcus aureus
CMCH	N-(2-Hydroxypropyl)-3-trimethylammonium chitosan chloride
TA	Tannic acid
E. coli	Escherichia coli
PEG	Polyethylene glycol
DEX	Dextran
SF	Silk fibroin
Col	Collagen
ALP	Alkaline phosphate
SPEEK	Sulfonated polyetheretherketone
AgNPs	Ag nanoparticles
CNF	Cellulose nanofibril
PDA	Polydopamine
SP NPs	Silver phosphate nanoparticles
MF	Melamine formaldehyde
PAH	Poly(allylamine hydrochloride)
PLO	Poly-L-ornithine
HA	Hyaluronic acid
MSN	Mesoporous silica nanoparticle
TPPS4	5,10,15,20-Tetrakis(4-sulfonatophenyl)-porphyrin
PAMAM	Polyamidoamine
PGMA	Polyglycerol methacrylate
PEI	Polyethyleneimine
HPs	Hedgehog-shaped particles
SERS	Surface-enhanced Raman scattering
Fmoc-FF	N-Fluorenylmethoxycarbonyl diphenylalanine
EGCG	Epigallocatechin gallate
ssDNA	Single-stranded DNA
HAp	Hydroxyapatite
PLLA	Poly-L-lactic acid
PMMA	Poly(methylmethacrylate)
Dox	Doxorubicin
SPBs	Semiconducting polymer brushes
Dex	Dexamethasone
5FU	5-Fluorouracil
PLGA	Poly(D,L-lactide-co-glycolide)
PLH	Poly-L-histidine
PEG-b-PLG	Poly(ethylene glycol)-block-poly(L-glutamic acid)

Author contributions

Lin Cao collected literature, wrote the first draft, and made subsequent modifications. Yanqi Huang provided support for literature collection and the first draft on the content of nanostructures for encapsulation and related applications. Bogdan V. Parakhonskiy and Andre G. Skirtach coordinated and organized this work, and provided valuable suggestions for improving the framework of the review and the final draft. Finally, all authors have contributed materially and intellectually through several joint papers on the development of self-assembly to nanoarchitectonics, which helped to shape its intellectual basis.

Conflicts of interest

The authors declare no conflict of interest.

Acknowledgements

This work is supported by the China Scholarship Council (CSC No. 202106910013 and 202006370040). This work is supported by FWO (Research Foundation Flanders): G043219N, G043322N, I002620N, and BOF-UGent: 01IO3618. This project has also received funding from FWO-F.N.R.S. under the Excellence of Science (EOS) program, grant number: 40007488. We would like to thank the Faculty of Bioscience Engineering, Department of Biotechnology of Ghent University for providing a good research platform.

References

1. M. J. Adler, in Aristotle for Everybody, Simon and Schuster, 1997.
2. G. E. Smith, J. Anat., 1927, 61, 264–266.
3. C. C. Hilgetag, S. F. Beul, S. J. van Albada and A. Goulas, Netw. Neurosci., 2019, 3, 905–923.
4. M. Aono and K. Ariga, Adv. Mater., 2016, 28, 989–992.
5. D. Lin, Y. Liu, A. Pei and Y. Cui, Nano Res., 2017, 10, 4003–4026.
6. J. Wan, S. D. Lacey, J. Dai, W. Bao, M. S. Fuhrer and L. Hu, Chem. Soc. Rev., 2016, 45, 6742–6765.
7. Y. Wu, H. Pang, Y. Liu, X. Wang, S. Yu, D. Fu, J. Chen and X. Wang, Environ. Pollut., 2019, 246, 608–620.
8. F. Lu and D. Astruc, Coord. Chem. Rev., 2020, 408, 213180.
9. A. Beck, L. Goetsch, C. Dumontet and N. Corvaïa, Nat. Rev. Drug Discovery, 2017, 16, 315–337.
10. J. Shi, P. W. Kantoff, R. Wooster and O. C. Farokhzad, Nat. Rev. Cancer, 2017, 17, 20–37.
11. K. Ariga, X. Jia, J. Song, J. P. Hill, D. T. Leong, Y. Jia and J. Li, Angew. Chem., Int. Ed., 2020, 59, 15424–15446.
12. C. Chircov and A. M. Grumezescu, Nanoarchitectonics in Biomedicine, Elsevier, 2019, pp. 1–21.
13. H. Noh, C.-W. Kung, T. Islamoglu, A. W. Peters, Y. Liao, P. Li, S. J. Garibay, X. Zhang, M. R. DeStefano, J. T. Hupp and O. K. Farha, Chem. Mater., 2018, 30, 2193–2197.
14. J. Fichtner, S. Watzele, B. Garlyyev, R. M. Kluge, F. Haimerl, H. A. El-Sayed, W.-J. Li, F. M. Maillard, L. Dubau, R. Chattot, J. Michalička, J. M. Macak, W. Wang, D. Wang, T. Gigl, C. Hugenschmidt and A. S. Bandarenka, ACS Catal., 2020, 10, 3131–3142.
15. I. Ijaz, E. Gilani, A. Nazir and A. Bukhari, Green Chem. Lett. Rev., 2020, 13, 223–245.
16. E. S. Madivoli, P. G. Kareru, A. N. Gachanja, D. S. Makhanu and S. M. Mugo, J. Inorg. Organomet. Polym., 2022, 32, 854–863.
17. C. Jia, C. Chen, Y. Kuang, K. Fu, Y. Wang, Y. Yao, S. Kronthal, E. Hitz, J. Song, F. Xu, B. Liu and L. Hu, Adv. Mater., 2018, 30, 1801347.
18. K. Ariga and Y. Yamauchi, Chem. – Asian J., 2020, 15, 718–728.
19. T. Hasegawa, K. Terabe, T. Tsuruoka and M. Aono, Adv. Mater., 2012, 24, 252–267.
20. Y. Dong, S. Zhang, Z. Wu, X. Li, W. L. Wang, Y. Zhu, S. Stoilova-McPhie, Y. Lu, D. Finley and Y. Mao, Nature, 2019, 565, 49–55.
21. W. Cui, A. Wang, J. Zhao and J. Li, Adv. Colloid Interface Sci., 2016, 237, 43–51.
22. F. Würthner, C. R. Saha-Möller, B. Fimmel, S. Ogi, P. Leowanawat and D. Schmidt, Chem. Rev., 2016, 116, 962–1052.
23. G. M. Whitesides and B. Grzybowski, Science, 2002, 295, 2418–2421.
24. K. Ariga and J. Li, Adv. Mater., 2016, 28, 987–988.
25. K. Ariga, Q. Ji, W. Nakanishi, J. P. Hill and M. Aono, Mater. Horiz., 2015, 2, 406–413.
26. K. Ariga, M. Li, G. J. Richards and J. P. Hill, J. Nanosci. Nanotechnol., 2011, 11, 1–13.
27. K. Ariga, J. Li, J. Fei, Q. Ji and J. P. Hill, Adv. Mater., 2016, 28, 1251–1286.
28. K. Ariga, Mater. Chem. Front., 2017, 1, 208–211.
29. K. Ariga, M. Nishikawa, T. Mori, J. Takeya, L. K. Shrestha and J. P. Hill, Sci. Technol. Adv. Mater., 2019, 20, 51–95.
30. K. Ariga, T. Mori, T. Kitao and T. Uemura, Adv. Mater., 2020, 32, 1905657.
31. Z. Sun, K. Ikemoto, T. M. Fukunaga, T. Koretsune, R. Arita, S. Sato and H. Isobe, Science, 2019, 363, 151–155.
32. T. Mori, H. Tanaka, A. Dalui, N. Mitoma, K. Suzuki, M. Matsumoto, N. Aggarwal, A. Patnaik, S. Acharya, L. K. Shrestha, H. Sakamoto, K. Itami and K. Ariga, Angew. Chem., 2018, 130, 9827–9831.
33. K. Ariga, M. Ito, T. Mori, S. Watanabe and J. Takeya, Nano Today, 2019, 28, 100762.
34. B. L. Li, M. I. Setyawati, L. Chen, J. Xie, K. Ariga, C.-T. Lim, S. Garaj and D. T. Leong, ACS Appl. Mater. Interfaces, 2017, 9, 15286–15296.
35. M. Gosak, R. Markovič, J. Dolenšek, M. Slak Rupnik, M. Marhl, A. Stožer and M. Perc, Phys. Life Rev., 2018, 24, 118–135.
36. K. Ariga, Y. Lvov and G. Decher, Phys. Chem. Chem. Phys., 2022, 24, 4097–4115.
37. J. Na, D. Zheng, J. Kim, M. Gao, A. Azhar, J. Lin and Y. Yamauchi, Small, 2022, 18, 2102397.
38. S. Li, Q. Zou, R. Xing, T. Govindaraju, R. Fakhrullin and X. Yan, Theranostics, 2019, 9, 3249–3261.
39. M.-P. Pileni, Acc. Chem. Res., 2007, 40, 685–693.
40. A. G. Skirtach, C. Déjugnat, D. Braun, A. S. Susha, A. L. Rogach and G. B. Sukhorukov, J. Phys. Chem. C, 2007, 111, 555–564.
41. B. V. Parakhonskiy, M. F. Bedard, T. V. Bukreeva, G. B. Sukhorukov, H. Möhwald and A. G. Skirtach, J. Phys. Chem. C, 2010, 114, 1996–2002.
42. J. Kopeček and J. Yang, Angew. Chem., Int. Ed., 2012, 51, 7396–7417.
43. A. C. Mendes, E. T. Baran, R. L. Reis and H. S. Azevedo, Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol., 2013, 5, 582–612.
44. M. A. Boles, M. Engel and D. V. Talapin, Chem. Rev., 2016, 116, 11220–11289.
45. Y. Lin, A. Böker, J. He, K. Sill, H. Xiang, C. Abetz, X. Li, J. Wang, T. Emrick, S. Long, Q. Wang, A. Balazs and T. P. Russell, Nature, 2005, 434, 55–59.
46. M. P. Stoykovich, H. Kang, K. C. Daoulas, G. Liu, C.-C. Liu, J. J. de Pablo, M. Müller and P. F. Nealey, ACS Nano, 2007, 1, 168–175.
47. P. Yin, H. M. T. Choi, C. R. Calvert and N. A. Pierce, Nature, 2008, 451, 318–322.
48. K. H. Smith, E. Tejeda-Montes, M. Poch and A. Mata, Chem. Soc. Rev., 2011, 40, 4563.
49. T. P. Bigioni, X.-M. Lin, T. T. Nguyen, E. I. Corwin, T. A. Witten and H. M. Jaeger, Nat. Mater., 2006, 5, 265–270.
50. J. Zhuang, H. Wu, Y. Yang and Y. C. Cao, J. Am. Chem. Soc., 2007, 129, 14166–14167.
51. E. Rabani, D. R. Reichman, P. L. Geissler and L. E. Brus, Nature, 2003, 426, 271–274.
52. D. V. Talapin, E. V. Shevchenko, C. B. Murray, A. V. Titov and P. Král, Nano Lett., 2007, 7, 1213–1219.
53. D. Zherebetskyy, M. Scheele, Y. Zhang, N. Bronstein, C. Thompson, D. Britt, M. Salmeron, P. Alivisatos and L.-W. Wang, Science, 2014, 344, 1380–1384.
54. S. Fischer, A. Salcher, A. Kornowski, H. Weller and S. Förster, Angew. Chem., 2011, 123, 7957–7960.
55. Y. Liu, Y. Li, J. He, K. J. Duelge, Z. Lu and Z. Nie, J. Am. Chem. Soc., 2014, 136, 2602–2610.
56. R. L. Marson, T. D. Nguyen and S. C. Glotzer, MRS Commun., 2015, 5, 397–406.
57. B. Cabane, J. Li, F. Artzner, R. Botet, C. Labbez, G. Bareigts, M. Sztucki and L. Goehring, Phys. Rev. Lett., 2016, 116, 208001.
58. Z. Tang, N. A. Kotov and M. Giersig, Science, 2002, 297, 237–240.
59. R. Jin, G. Wu, Z. Li, C. A. Mirkin and G. C. Schatz, J. Am. Chem. Soc., 2003, 125, 1643–1654.
60. T. I. N. G. Li, R. Sknepnek and M. Olvera de la Cruz, J. Am. Chem. Soc., 2013, 135, 8535–8541.
61. R. Klajn, J. F. Stoddart and B. A. Grzybowski, Chem. Soc. Rev., 2010, 39, 2203.
62. M. I. Bodnarchuk, M. V. Kovalenko, W. Heiss and D. V. Talapin, J. Am. Chem. Soc., 2010, 132, 11967–11977.
63. J.-C. Cheng, L.-Y. Pan, X.-L. Huang, Y.-P. Huang, Y.-H. Wang, S.-P. Xu, F.-F. Li, Z.-W. Men and T. Cui, Nanomaterials, 2021, 11, 325.
64. S.-Y. Zhang, M. D. Regulacio and M.-Y. Han, Chem. Soc. Rev., 2014, 43, 2301.
65. A. Sánchez-Iglesias, M. Grzelczak, T. Altantzis, B. Goris, J. Pérez-Juste, S. Bals, G. Van Tendeloo, S. H. Donaldson, B. F. Chmelka, J. N. Israelachvili and L. M. Liz-Marzán, ACS Nano, 2012, 6, 11059–11065.
66. Z. Nie and E. Kumacheva, Nat. Mater., 2008, 7, 277–290.
67. J. Spatz, S. Mößmer, M. Möller, M. Kocher, D. Neher and G. Wegner, Adv. Mater., 1998, 10, 473–475.
68. S. Mann and G. Ozin, Nature, 1996, 382, 313–318.
69. J. He, R. Tangirala, T. Emrick, T. P. Russell, A. Böker, X. Li and J. Wang, Adv. Mater., 2007, 19, 381–385.
70. K. Ariga, Y. Yamauchi, T. Mori and J. P. Hill, Adv. Mater., 2013, 25, 6477–6512.
71. S. A. Hussain, B. Dey, D. Bhattacharjee and N. Mehta, Heliyon, 2018, 4, e01038.
72. M. Ito, Y. Yamashita, Y. Tsuneda, T. Mori, J. Takeya, S. Watanabe and K. Ariga, ACS Appl. Mater. Interfaces, 2020, 12, 56522–56529.
73. F. Gür, E. D. Kaya, B. Gür, A. Türkhan and Y. Onganer, Colloids Surf., A, 2019, 583, 124005.
74. D. D. Lasic and D. Papahadjopoulos, Science, 1995, 267, 1275–1276.
75. J. N. Israelachvili, S. Marčelja and R. G. Horn, Q. Rev. Biophys., 1980, 13, 121–200.
76. P. S. Zangabad, S. Mirkiani, S. Shahsavari, B. Masoudi, M. Masroor, H. Hamed, Z. Jafari, Y. D. Taghipour, H. Hashemi, M. Karimi and M. R. Hamblin, Nanotechnol. Rev., 2018, 7, 95–122.
77. A. Laouini, C. Jaafar-Maalej, I. Limayem-Blouza, S. Sfar, C. Charcosset and H. Fessi, J. Colloid Sci. Biotechnol., 2012, 1, 147–168.
78. W. Zhou, W. Liu, L. Zou, W. Liu, C. Liu, R. Liang and J. Chen, Colloids Surf., B, 2014, 117, 330–337.
79. K. Son, M. Ueda, K. Taguchi, T. Maruyama, S. Takeoka and Y. Ito, J. Controlled Release, 2020, 322, 209–216.
80. A. D. Bangham, Chem. Phys. Lipids, 1993, 64, 275–285.
81. H. Daraee, A. Etemadi, M. Kouhi, S. Alimirzalu and A. Akbarzadeh, Artif. Cells, Nanomed., Biotechnol., 2016, 44, 381–391.
82. M. Celestin, S. Krishnan, S. Bhansali, E. Stefanakos and D. Y. Goswami, Nano Res., 2014, 7, 589–625.
83. D. Guimarães, A. Cavaco-Paulo and E. Nogueira, Int. J. Pharm., 2021, 601, 120571.
84. M. V. Kovalenko, M. Scheele and D. V. Talapin, Science, 2009, 324, 1417–1420.
85. C. R. Kagan, E. Lifshitz, E. H. Sargent and D. V. Talapin, Science, 2016, 353, aac5523.
86. Y. Shi, D. Wan, J. Huang, Y. Liu and J. Li, Chemosphere, 2020, 252, 126581.
87. K. Manabe, Prog. Org. Coat., 2020, 142, 105599.
88. T. Sen, B. Ozcelik and M. M. Ozmen, Int. J. Polym. Mater. Polym. Biomater., 2019, 68, 411–416.
89. R. K. Kramer, F. E. G. Guimarães and A. J. F. Carvalho, J. Mol. Liq., 2019, 273, 368–373.
90. T. A. Kolesnikova, D. Kohler, A. G. Skirtach and H. Möhwald, ACS Nano, 2012, 6, 9585–9595.
91. M. F. Bédard, B. G. De Geest, H. Möhwald, G. B. Sukhorukov and A. G. Skirtach, Soft Matter, 2009, 5, 3297–3931.
92. D. V. Talapin, J.-S. Lee, M. V. Kovalenko and E. V. Shevchenko, Chem. Rev., 2010, 110, 389–458.
93. K. Ariga, Y. Yamauchi, G. Rydzek, Q. Ji, Y. Yonamine, K. C.-W. Wu and J. P. Hill, Chem. Lett., 2014, 43, 36–68.
94. M. S. Saveleva, K. Eftekhari, A. Abalymov, T. E. L. Douglas, D. Volodkin, B. V. Parakhonskiy and A. G. Skirtach, Front. Chem., 2019, 7, 179.
95. M. A. C. Stuart, W. T. S. Huck, J. Genzer, M. Müller, C. Ober, M. Stamm, G. B. Sukhorukov, I. Szleifer, V. V. Tsukruk, M. Urban, F. Winnik, S. Zauscher, I. Luzinov and S. Minko, Nat. Mater., 2010, 9, 101–113.
96. S. T. Milner, Science, 1991, 251, 905–914.
97. O. Azzaroni, J. Polym. Sci., Part A: Polym. Chem., 2012, 50, 3225–3258.
98. C. Feng and X. Huang, Acc. Chem. Res., 2018, 51, 2314–2323.
99. P. Brandani and P. Stroeve, Macromolecules, 2003, 36, 9492–9501.
100. M. Divandari, G. Morgese, S. N. Ramakrishna and E. M. Benetti, Eur. Polym. J., 2019, 110, 301–306.
101. S. Zapotoczny, Surface-Grafted Polymer Brushes, in Biomaterials Surface Science, ed. A. Taubert, J. F Mano and C. Rodriguez-Cabello, Wiley-VCH, Verlag GmbH & Co. KGaA, 2013, pp. 27–43.
102. A. J. Wójcik, K. Wolski and S. Zapotoczny, Eur. Polym. J., 2021, 155, 110577.
103. B. Zhao and W. J. Brittain, Prog. Polym. Sci., 2000, 25, 677–710.
104. B. M. D. O'Driscoll, G. H. Griffiths, M. W. Matsen, S. Perrier, V. Ladmiral and I. W. Hamley, Macromolecules, 2010, 43, 8177–8184.
105. E. B. Zhulina, C. Singh and A. C. Balazs, Macromolecules, 1996, 29, 6338–6348.
106. Y. Yin, P. Sun, B. Li, T. Chen, Q. Jin, D. Ding and A.-C. Shi, Macromolecules, 2007, 40, 5161–5170.
107. C. Feng, Y. Li, D. Yang, J. Hu, X. Zhang and X. Huang, Chem. Soc. Rev., 2011, 40, 1282–1295.
108. T. Zhou, H. Qi, L. Han, D. Barbash and C. Y. Li, Nat. Commun., 2016, 7, 11119.
109. Y. Zhai, X. Chen, Z. Yuan, X. Han and H. Liu, Polym. Chem., 2020, 11, 4622–4629.
110. A. M. Jonas, K. Glinel, R. Oren, B. Nysten and W. T. S. Huck, Macromolecules, 2007, 40, 4403–4405.
111. L. Ionov, V. Bocharova and S. Diez, Soft Matter, 2009, 5, 67–71.
112. A. Steinhaus, T. Pelras, R. Chakroun, A. H. Gröschel and M. Müllner, Macromol. Rapid Commun., 2018, 39, 1800177.
113. T. Pelras, C. S. Mahon and M. Müllner, Angew. Chem., Int. Ed., 2018, 57, 6982–6994.
114. G. Decher, Science, 1997, 277, 1232–1237.
115. W. Xu, A. A. Steinschulte, F. A. Plamper, V. F. Korolovych and V. V. Tsukruk, Chem. Mater., 2016, 28, 975–985.
116. W. Xu, P. A. Ledin, Z. Iatridi, C. Tsitsilianis and V. V. Tsukruk, Angew. Chem., Int. Ed., 2016, 55, 4908–4913.
117. J. J. Richardson, M. Björnmalm and F. Caruso, Science, 2015, 348, aaa2491.
118. O. Löhmann, M. Zerball and R. von Klitzing, Langmuir, 2018, 34, 11518–11525.
119. A. Baba, P. Taranekar, R. R. Ponnapati, W. Knoll and R. C. Advincula, ACS Appl. Mater. Interfaces, 2010, 2, 2347–2354.
120. K. Ariga, M. Nishikawa, T. Mori, J. Takeya, L. K. Shrestha and J. P. Hill, Sci. Technol. Adv. Mater., 2019, 20, 51–95.
121. M. Delcea, H. Möhwald and A. G. Skirtach, Adv. Drug Delivery Rev., 2011, 63, 730–747.
122. C. Picart, J. Mutterer, L. Richert, Y. Luo, G. D. Prestwich, P. Schaaf, J.-C. Voegel and P. Lavalle, Proc. Natl. Acad. Sci. U. S. A., 2002, 99, 12531–12535.
123. S. A. Sukhishvili, E. Kharlampieva and V. Izumrudov, Macromolecules, 2006, 39, 8873–8881.
124. J. J. Richardson, J. Cui, M. Björnmalm, J. A. Braunger, H. Ejima and F. Caruso, Chem. Rev., 2016, 116, 14828–14867.
125. E. V. Musin, A. L. Kim, A. V. Dubrovskii and S. A. Tikhonenko, Sci. Rep., 2021, 11, 14040.
126. K. Ariga, E. Ahn, M. Park and B. Kim, Chem. – Asian J., 2019, 14, 2553–2566.
127. W. B. Stockton and M. F. Rubner, Macromolecules, 1997, 30, 2717–2725.
128. E. Kharlampieva, V. Kozlovskaya and S. A. Sukhishvili, Adv. Mater., 2009, 21, 3053–3065.
129. J. F. Quinn and F. Caruso, Adv. Funct. Mater., 2006, 16, 1179–1186.
130. Y. Lvov, K. Ariga, I. Ichinose and T. Kunitake, J. Chem. Soc., Chem. Commun., 1995, 2313.
131. Y. Shimazaki, M. Mitsuishi, S. Ito and M. Yamamoto, Langmuir, 1997, 13, 1385–1387.
132. M. Li, S. Ishihara, M. Akada, M. Liao, L. Sang, J. P. Hill, V. Krishnan, Y. Ma and K. Ariga, J. Am. Chem. Soc., 2011, 133, 7348–7351.
133. H. Xiong, M. Cheng, Z. Zhou, X. Zhang and J. Shen, Adv. Mater., 1998, 10, 529–532.
134. T. Serizawa, K. Hamada and M. Akashi, Nature, 2004, 429, 52–55.
135. I. Ichinose, H. Senzu and T. Kunitake, Chem. Mater., 1997, 9, 1296–1298.
136. J. Borges and J. F. Mano, Chem. Rev., 2014, 114, 8883–8942.
137. J. Chen, L. Huang, L. Ying, G. Luo, X. Zhao and W. Cao, Langmuir, 1999, 15, 7208–7212.
138. A. A. Antipov, G. B. Sukhorukov, E. Donath and H. Möhwald, J. Phys. Chem. B, 2001, 105, 2281–2284.
139. S. E. Burke and C. J. Barrett, Biomacromolecules, 2003, 4, 1773–1783.
140. K. Yoshida, K. Suwa and J. Anzai, Materials, 2016, 9, 425.
141. J. M. Silva, S. G. Caridade, R. R. Costa, N. M. Alves, T. Groth, C. Picart, R. L. Reis and J. F. Mano, Langmuir, 2015, 31, 11318–11328.
142. S. T. Dubas and J. B. Schlenoff, Langmuir, 2001, 17, 7725–7727.
143. S. T. Dubas and J. B. Schlenoff, Macromolecules, 1999, 32, 8153–8160.
144. D. Laurent and J. B. Schlenoff, Langmuir, 1997, 13, 1552–1557.
145. R. Steitz, W. Jaeger and R. v. Klitzing, Langmuir, 2001, 17, 4471–4474.
146. C.-A. Ghiorghita, F. Bucatariu and E. S. Dragan, Mater. Sci. Eng., C, 2019, 105, 110050.
147. F.-X. Xiao, M. Pagliaro, Y.-J. Xu and B. Liu, Chem. Soc. Rev., 2016, 45, 3088–3121.
148. P. Schaaf, J.-C. Voegel, L. Jierry and F. Boulmedais, Adv. Mater., 2012, 24, 1001–1016.
149. M. V. Zyuzin, A. S. Timin and G. B. Sukhorukov, Langmuir, 2019, 35, 4747–4762.
150. U. Kreibig and M. Vollmer, in Optical Properties of Metal Clusters, Springer Science & Business Media, 2013.
151. S. Lu, M. Li, D. Liu, Y. Yang and P. Yang, J. Nanosci. Nanotechnol., 2018, 18, 288–295.
152. D. Zhang, C. Jiang, P. Li and Y. Sun, ACS Appl. Mater. Interfaces, 2017, 9, 6462–6471.
153. G. H. S. Rodrigues, C. M. Miyazaki, R. J. G. Rubira, C. J. L. Constantino and M. Ferreira, ACS Appl. Nano Mater., 2019, 2, 1082–1091.
154. T. Panapimonlawat, S. Phanichphant and S. Sriwichai, Polymer, 2021, 13, 1488.
155. B.-S. Kim, S. W. Park and P. T. Hammond, ACS Nano, 2008, 2, 386–392.
156. J. Zhang, D. Wang, X. Jiang, L. He, L. Fu, Y. Zhao, Y. Wang, H. Mo and J. Shen, Chem. Eng. J., 2019, 370, 1057–1067.
157. T. Mohan, R. Kargl, K. E. Tradt, M. R. Kulterer, M. Braćić, S. Hribernik, K. Stana-Kleinschek and V. Ribitsch, Carbohydr. Polym., 2015, 116, 149–158.
158. P. F. Ferrari, E. Zattera, L. Pastorino, P. Perego and D. Palombo, Int. J. Biol. Macromol., 2021, 177, 548–558.
159. M. Kumorek, I. M. Minisy, T. Krunclová, M. Voršiláková, K. Venclíková, E. M. Chánová, O. Janoušková and D. Kubies, Mater. Sci. Eng., C, 2020, 109, 110493.
160. T. G. Shutava, K. S. Livanovich and A. A. Sharamet, Colloids Surf., B, 2019, 173, 412–420.
161. S. Nawae, J. Meesane, N. Muensit and C. Daengngam, Mater. Des., 2018, 160, 1158–1167.
162. X. Arys, A. Laschewsky and A. M. Jonas, Macromolecules, 2001, 34, 3318–3330.
163. K. Glinel, A. Laschewsky and A. M. Jonas, Macromolecules, 2001, 34, 5267–5274.
164. M. Szuwarzyński, K. Wolski, T. Kruk and S. Zapotoczny, Prog. Polym. Sci., 2021, 121, 101433.
165. Y. Deng, L. Yang, X. Huang, J. Chen, X. Shi, W. Yang, M. Hong, Y. Wang, M. S. Dargusch and Z. Chen, Macromol. Biosci., 2018, 18, 1800028.
166. Q. Chen, C. J. Brett, A. Chumakov, M. Gensch, M. Schwartzkopf, V. Körstgens, L. D. Söderberg, A. Plech, P. Zhang, P. Müller-Buschbaum and S. V. Roth, ACS Appl. Nano Mater., 2021, 4, 503–513.
167. M. Li, X. Liu, Z. Xu, K. W. K. Yeung and S. Wu, ACS Appl. Mater. Interfaces, 2016, 8, 33972–33981.
168. E. Donath, G. B. Sukhorukov, F. Caruso, S. A. Davis and H. Möhwald, Angew. Chem., Int. Ed., 1998, 37, 2201–2205.
169. F. Caruso, R. A. Caruso and H. Möhwald, Science, 1998, 282, 1111–1114.
170. W. Tong, X. Song and C. Gao, Chem. Soc. Rev., 2012, 41, 6103.
171. A. J. Khopade and F. Caruso, Chem. Mater., 2004, 16, 2107–2112.
172. Q.-L. Li, Y. Sun, Y.-L. Sun, J. Wen, Y. Zhou, Q.-M. Bing, L. D. Isaacs, Y. Jin, H. Gao and Y.-W. Yang, Chem. Mater., 2014, 26, 6418–6431.
173. Z. Wang, X. Zhang, J. Gu, H. Yang, J. Nie and G. Ma, Carbohydr. Polym., 2014, 103, 38–45.
174. M. Porta-i-Batalla, C. Eckstein, E. Xifré-Pérez, P. Formentín, J. Ferré-Borrull and L. F. Marsal, Nanoscale Res. Lett., 2016, 11, 372.
175. P. Wang, R. K. Kankala, J. Fan, R. Long, Y. Liu and S. Wang, J. Mater. Sci. Mater. Med., 2018, 29, 68.
176. S. Aslan, M. Deneufchatel, S. Hashmi, N. Li, L. D. Pfefferle, M. Elimelech, E. Pauthe and P. R. Van Tassel, J. Colloid Interface Sci., 2012, 388, 268–273.
177. A. M. Yashchenok, D. N. Bratashov, D. A. Gorin, M. V. Lomova, A. M. Pavlov, A. V. Sapelkin, B. S. Shim, G. B. Khomutov, N. A. Kotov, G. B. Sukhorukov, H. Möhwald and A. G. Skirtach, Adv. Funct. Mater., 2010, 20, 3136–3142.
178. L. Li, K. K. Sun, L. Fan, W. Hong, Z. S. Xu and L. Liu, Mater. Lett., 2014, 126, 197–201.
179. Y. Chen, Z. Xiong, L. Peng, Y. Gan, Y. Zhao, J. Shen, J. Qian, L. Zhang and W. Zhang, ACS Appl. Mater. Interfaces, 2015, 7, 16338–16347.
180. R. Ladj, A. Bitar, M. M. Eissa, H. Fessi, Y. Mugnier, R. Le Dantec and A. Elaissari, Int. J. Pharm., 2013, 458, 230–241.
181. K. Radhakrishnan, J. Tripathy, D. P. Gnanadhas, D. Chakravortty and A. M. Raichur, RSC Adv., 2014, 4, 45961–45968.
182. J. Campbell, J. Abnett, G. Kastania, D. Volodkin and A. S. Vikulina, ACS Appl. Mater. Interfaces, 2021, 13, 3259–3269.
183. I. Marchenko, A. Yashchenok, T. Borodina, T. Bukreeva, M. Konrad, H. Möhwald and A. Skirtach, J. Controlled Release, 2012, 162, 599–605.
184. F. Cuomo, F. Lopez, M. Piludu, M. G. Miguel, B. Lindman and A. Ceglie, J. Colloid Interface Sci., 2015, 447, 211–216.
185. Y. Tarakanchikova, A. Muslimov, I. Sergeev, K. Lepik, N. Yolshin, A. Goncharenko, K. Vasilyev, I. Eliseev, A. Bukatin, V. Sergeev, S. Pavlov, A. Popov, I. Meglinski, B. Afanasiev, B. Parakhonskiy, G. Sukhorukov and D. Gorin, J. Mater. Chem. B, 2020, 8, 9576–9588.
186. Y. Yang, H. Zhu, J. Wang, Q. Fang and Z. Peng, ACS Appl. Mater. Interfaces, 2018, 10, 33493–33506.
187. J. Zhou, G. Romero, E. Rojas, L. Ma, S. Moya and C. Gao, J. Colloid Interface Sci., 2010, 345, 241–247.
188. A. Yashchenok, B. Parakhonskiy, S. Donatan, D. Kohler, A. Skirtach and H. Möhwald, J. Mater. Chem. B, 2013, 1, 1223.
189. N. Balabushevich, E. Sholina, E. Mikhalchik, L. Filatova, A. Vikulina and D. Volodkin, Micromachines, 2018, 9, 307.
190. T. Paulraj, N. Feoktistova, N. Velk, K. Uhlig, C. Duschl and D. Volodkin, Macromol. Rapid Commun., 2014, 35, 1408–1413.
191. S. Belbekhouche, N. Bousserrhine, V. Alphonse and B. Carbonnier, Food Hydrocolloids, 2019, 95, 219–227.
192. X. Wang, Z. Jiang, J. Shi, Y. Liang, C. Zhang and H. Wu, ACS Appl. Mater. Interfaces, 2012, 4, 3476–3483.
193. B. G. De Geest, A. M. Jonas, J. Demeester and S. C. De Smedt, Langmuir, 2006, 22, 5070–5074.
194. D. Shi, M. Ran, H. Huang, L. Zhang, X. Li, M. Chen and M. Akashi, Polym. Chem., 2016, 7, 6779–6788.
195. W.-H. Chen, G.-F. Luo, W.-X. Qiu, Q. Lei, L.-H. Liu, S.-B. Wang and X.-Z. Zhang, Biomaterials, 2017, 117, 54–65.
196. J. Gauczinski, Z. Liu, X. Zhang and M. Schönhoff, Langmuir, 2012, 28, 4267–4273.
197. X. Xu, S. Lü, C. Gao, X. Bai, C. Feng, N. Gao and M. Liu, Mater. Des., 2015, 88, 1127–1133.
198. Y. Wu, Y. Long, Q.-L. Li, S. Han, J. Ma, Y.-W. Yang and H. Gao, ACS Appl. Mater. Interfaces, 2015, 7, 17255–17263.
199. J. Shi, L. Zhang and Z. Jiang, ACS Appl. Mater. Interfaces, 2011, 3, 881–889.
200. B. Amritha Rammohan, L. Tayal, A. Kumar, S. Sivakumar and A. Sharma, RSC Adv., 2013, 3, 2008–2016.
201. Y. Zhu, W. Tong, C. Gao and H. Möhwald, Langmuir, 2008, 24, 7810–7816.
202. D. G. Montjoy, J. H. Bahng, A. Eskafi, H. Hou and N. A. Kotov, J. Am. Chem. Soc., 2018, 140, 7835–7845.
203. S. T. Sivapalan, B. M. DeVetter, T. K. Yang, M. V. Schulmerich, R. Bhargava and C. J. Murphy, J. Phys. Chem. C, 2013, 117, 10677–10682.
204. L. Tang, T. Vo, X. Fan, D. Vecchio, T. Ma, J. Lu, H. Hou, S. C. Glotzer and N. A. Kotov, J. Am. Chem. Soc., 2021, 143, 19655–19667.
205. E. V. Lengert, S. I. Koltsov, J. Li, A. V. Ermakov, B. V. Parakhonskiy, E. V. Skorb and A. G. Skirtach, Coatings, 2020, 10, 1131.
206. M. Delcea, S. Schmidt, R. Palankar, P. A. L. Fernandes, A. Fery, H. Möhwald and A. G. Skirtach, Small, 2010, 6, 2858–2862.
207. M. F. Bédard, A. Munoz-Javier, R. Mueller, P. del Pino, A. Fery, W. J. Parak, A. G. Skirtach and G. B. Sukhorukov, Soft Matter, 2009, 5, 148–155.
208. W. J. Anderson, K. Nowinska, T. Hutter, S. Mahajan and M. Fischlechner, Nanoscale, 2018, 10, 7138–7146.
209. E. Lengert, M. Saveleva, A. Abalymov, V. Atkin, P. C. Wuytens, R. Kamyshinsky, A. L. Vasiliev, D. A. Gorin, G. B. Sukhorukov, A. G. Skirtach and B. Parakhonskiy, ACS Appl. Mater. Interfaces, 2017, 9, 21949–21958.
210. I. Y. Stetciura, A. V. Markin, A. N. Ponomarev, A. V. Yakimansky, T. S. Demina, C. Grandfils, D. V. Volodkin and D. A. Gorin, Langmuir, 2013, 29, 4140–4147.
211. D. Chen, Y. Zhang, T. Bessho, J. Sang, H. Hirahara, K. Mori and Z. Kang, Chem. Eng. J., 2016, 303, 100–108.
212. Y. Ju, C. Cortez-Jugo, J. Chen, T. Wang, A. J. Mitchell, E. Tsantikos, N. Bertleff-Zieschang, Y. Lin, J. Song, Y. Cheng, S. Mettu, M. A. Rahim, S. Pan, G. Yun, M. L. Hibbs, L. Y. Yeo, C. E. Hagemeyer and F. Caruso, Adv. Sci., 2020, 7, 1902650.
213. A. Mateos-Maroto, L. Fernández-Peña, I. Abelenda-Núñez, F. Ortega, R. G. Rubio and E. Guzmán, Polymer, 2022, 14, 479.
214. D. Volodkin, A. Skirtach and H. Möhwald, Polym. Int., 2012, 61, 673–679.
215. D. Volodkin, A. Skirtach and H. Möhwald, Bioactive Surfaces, Springer Berlin Heidelberg, 2010, vol. 240, pp. 135–161.
216. P. K. Vemula, N. Wiradharma, J. A. Ankrum, O. R. Miranda, G. John and J. M. Karp, Curr. Opin. Biotechnol., 2013, 24, 1174–1182.
217. X. Hu, Y. Wang, L. Zhang and M. Xu, Food Chem., 2020, 306, 125632.
218. Z. Shariatinia and A. Barzegari, Polysaccharide Carriers for Drug Delivery, Elsevier, 2019, pp. 639–684.
219. E. J. Bealer, S. Onissema-Karimu, A. Rivera-Galletti, M. Francis, J. Wilkowski, D. Salas-de la Cruz and X. Hu, Polymer, 2020, 12, 464.
220. G. Archana, K. Sabina, S. Babuskin, K. Radhakrishnan, M. A. Fayidh, P. A. S. Babu, M. Sivarajan and M. Sukumar, Carbohydr. Polym., 2013, 98, 89–94.
221. J. J. Panda and V. S. Chauhan, Polym. Chem., 2014, 5, 4431–4449.
222. H. Cui, N. Pan, W. Fan, C. Liu, Y. Li, Y. Xia and K. Sui, Adv. Funct. Mater., 2019, 29, 1807692.
223. B. Singh, S. Sharma and A. Dhiman, Carbohydr. Polym., 2017, 165, 294–303.
224. I. Tokarev and S. Minko, Soft Matter, 2009, 5, 511–524.
225. D. Kuckling, Colloid Polym. Sci., 2009, 287, 881–891.
226. B. Chollet, M. Li, E. Martwong, B. Bresson, C. Fretigny, P. Tabeling and Y. Tran, ACS Appl. Mater. Interfaces, 2016, 8, 11729–11738.
227. G. P. Sakala and M. Reches, Adv. Mater. Interfaces, 2018, 5, 1800073.
228. S. Yuran, A. Dolid and M. Reches, ACS Biomater. Sci. Eng., 2018, 4, 4051–4061.
229. M. Lian, X. Chen, Y. Lu and W. Yang, ACS Appl. Mater. Interfaces, 2016, 8, 25036–25042.
230. M. Righi, G. L. Puleo, I. Tonazzini, G. Giudetti, M. Cecchini and S. Micera, Sci. Rep., 2018, 8, 502.
231. P. Heidarian, A. Z. Kouzani, A. Kaynak, M. Paulino, B. Nasri-Nasrabadi, A. Zolfagharian and R. Varley, Carbohydr. Polym., 2020, 231, 115743.
232. S. Trombino, C. Servidio, F. Curcio and R. Cassano, Pharmaceutics, 2019, 11, 407.
233. X. Hu, L. Yan, Y. Wang and M. Xu, Chem. Eng. J., 2020, 388, 124189.
234. X. Hu, Y. Wang, L. Zhang and M. Xu, Carbohydr. Polym., 2020, 234, 115920.
235. Y. Xiong, K. Yan, W. E. Bentley, H. Deng, Y. Du, G. F. Payne and X.-W. Shi, ACS Appl. Mater. Interfaces, 2014, 6, 2948–2957.
236. M. Marquis, J. Davy, B. Cathala, A. Fang and D. Renard, Carbohydr. Polym., 2015, 116, 189–199.
237. A. Abalymov, E. Lengert, L. Van der Meeren, M. Saveleva, A. Ivanova, T. E. L. Douglas, A. G. Skirtach, D. Volodkin and B. Parakhonskiy, Biomater. Adv., 2022, 133, 112632.
238. A. Abalymov, L. Van Poelvoorde, V. Atkin, A. G. Skirtach, M. Konrad and B. Parakhonskiy, ACS Appl. Bio Mater., 2020, 3, 2986–2996.
239. T. Wu, J. Huang, Y. Jiang, Y. Hu, X. Ye, D. Liu and J. Chen, Food Chem., 2018, 240, 361–369.
240. S. D. Hujaya, G. S. Lorite, S. J. Vainio and H. Liimatainen, Acta Biomater., 2018, 75, 346–357.
241. V. Kozlovskaya and E. Kharlampieva, Macromol. Biosci., 2022, 22, 2100328.
242. R. Xing, S. Li, N. Zhang, G. Shen, H. Möhwald and X. Yan, Biomacromolecules, 2017, 18, 3514–3523.
243. M. Goktas, G. Cinar, I. Orujalipoor, S. Ide, A. B. Tekinay and M. O. Guler, Biomacromolecules, 2015, 16, 1247–1258.
244. N. C. Wickremasinghe, V. A. Kumar and J. D. Hartgerink, Biomacromolecules, 2014, 15, 3587–3595.
245. H. Huang, A. I. Herrera, Z. Luo, O. Prakash and X. S. Sun, Biophys. J., 2012, 103, 979–988.
246. D. J. Adams, M. F. Butler, W. J. Frith, M. Kirkland, L. Mullen and P. Sanderson, Soft Matter, 2009, 5, 1856.
247. Y. Bai, Q. Luo and J. Liu, Chem. Soc. Rev., 2016, 45, 2756–2767.
248. H. Nakamura, Q. Rev. Biophys., 1996, 29, 1–90.
249. K. Stapelfeldt, S. Stamboroski, P. Mednikova and D. Brüggemann, Biofabrication, 2019, 11, 025010.
250. N. Suter, A. Joshi, T. Wunsch, N. Graupner, K. Stapelfeldt, M. Radmacher, J. Müssig and D. Brüggemann, Mater. Sci. Eng., C, 2021, 126, 112156.
251. D. Hense, A. Büngeler, F. Kollmann, M. Hanke, A. Orive, A. Keller, G. Grundmeier, K. Huber and O. I. Strube, Biomacromolecules, 2021, 22, 4084–4094.
252. K. Stapelfeldt, S. Stamboroski, I. Walter, N. Suter, T. Kowalik, M. Michaelis and D. Brüggemann, Nano Lett., 2019, 19, 6554–6563.
253. M. Kenny, S. Stamboroski, R. Taher, D. Brüggemann and I. Schoen, Adv. Healthcare Mater., 2022, 11, 2200249.
254. S. Das, K. Zhou, D. Ghosh, N. N. Jha, P. K. Singh, R. S. Jacob, C. C. Bernard, D. I. Finkelstein, J. S. Forsythe and S. K. Maji, NPG Asia Mater., 2016, 8, e304–e304.
255. R. S. Jacob, D. Ghosh, P. K. Singh, S. K. Basu, N. N. Jha, S. Das, P. K. Sukul, S. Patil, S. Sathaye, A. Kumar, A. Chowdhury, S. Malik, S. Sen and S. K. Maji, Biomaterials, 2015, 54, 97–105.
256. S.-C. How, T.-H. Lin, C.-C. Chang and S. S.-S. Wang, Int. J. Biol. Macromol., 2021, 184, 79–91.
257. B. Hu, Y. Shen, J. Adamcik, P. Fischer, M. Schneider, M. J. Loessner and R. Mezzenga, ACS Nano, 2018, 12, 3385–3396.
258. B. Hu, M. Li, X. He, H. Wang, J. Huang, Z. Liu and R. Mezzenga, Biomater. Sci., 2022, 10, 3597–3611.
259. V. Morya, S. Walia, B. B. Mandal, C. Ghoroi and D. Bhatia, ACS Biomater. Sci. Eng., 2020, 6, 6021–6035.
260. M. D. Frank-Kamenetskii, V. V. Anshelevich and A. V. Lukashin, Sov. Phys. Usp., 1987, 30, 317.
261. Y. Xing, E. Cheng, Y. Yang, P. Chen, T. Zhang, Y. Sun, Z. Yang and D. Liu, Adv. Mater., 2011, 23, 1117–1121.
262. Y. Ma, H. Liu, Q. Mou, D. Yan, X. Zhu and C. Zhang, Nanoscale, 2018, 10, 8367–8371.
263. S. Hu, X. Du, Y. Bi, P.-P. He, Y. Mu, C. Liu, Q. Gao, M. Yin and W. Guo, ACS Appl. Polym. Mater., 2022, 4, 5199–5208.
264. J. Gačanin, C. V. Synatschke and T. Weil, Adv. Funct. Mater., 2020, 30, 1906253.
265. S. Xia, S. Song, X. Ren and G. Gao, Soft Matter, 2017, 13, 6059–6067.
266. Y. Huang, L. Cao, B. V. Parakhonskiy and A. G. Skirtach, Pharmaceutics, 2022, 14, 909.
267. X. Hu, G. Nian, X. Liang, L. Wu, T. Yin, H. Lu, S. Qu and W. Yang, ACS Appl. Mater. Interfaces, 2019, 11, 10292–10300.
268. C. Pan, L. Liu, Q. Chen, Q. Zhang and G. Guo, ACS Appl. Mater. Interfaces, 2017, 9, 38052–38061.
269. N. Sarkar, G. Sahoo and S. K. Swain, Nano-Struct. Nano-Objects, 2020, 23, 100507.
270. I. M. Garnica-Palafox, H. O. Estrella-Monroy, N. A. Vázquez-Torres, M. Álvarez-Camacho, A. E. Castell-Rodríguez and F. M. Sánchez-Arévalo, Carbohydr. Polym., 2020, 236, 115971.
271. A. Abalymov, L. Van der Meeren, M. Saveleva, E. Prikhozhdenko, K. Dewettinck, B. Parakhonskiy and A. G. Skirtach, ACS Biomater. Sci. Eng., 2020, 6, 3933–3944.
272. A. Abalymov, L. Van der Meeren, D. Volodkin, B. Parakhonskiy and A. G. Skirtach, C, 2021, 7, 18.
273. Y. Zhuang, F. Yu, H. Chen, J. Zheng, J. Ma and J. Chen, J. Mater. Chem. A, 2016, 4, 10885–10892.
274. J. Zheng, P. Xiao, W. Liu, J. Zhang, Y. Huang and T. Chen, Macromol. Rapid Commun., 2016, 37, 265–270.
275. I. Lisiecki and M.-P. Pileni, J. Phys. Chem. C, 2012, 116, 3–14.
276. Q. Shi, W. Di, D. Dong, L. W. Yap, L. Li, D. Zang and W. Cheng, ACS Nano, 2019, 13, 5243–5250.
277. K. Mukai, M. Hara, S. Nagano and T. Seki, Angew. Chem., Int. Ed., 2016, 55, 14028–14032.
278. F.-X. Xiao, J. Miao and B. Liu, J. Am. Chem. Soc., 2014, 136, 1559–1569.
279. Y. H. Deng, J. H. Chen, Q. Yang and Y. Z. Zhuo, Chem. Eng. Res. Des., 2021, 170, 423–433.
280. A. G. Skirtach, D. V. Volodkin and H. Möhwald, ChemPhysChem, 2010, 11, 822–829.
281. E. Kilic, M. V. Novoselova, S. H. Lim, N. A. Pyataev, S. I. Pinyaev, O. A. Kulikov, O. A. Sindeeva, O. A. Mayorova, R. Murney, M. N. Antipina, B. Haigh, G. B. Sukhorukov and M. V. Kiryukhin, Sci. Rep., 2017, 7, 44159.
282. J. Li, D. Khalenkow, D. Volodkin, A. Lapanje, A. G. Skirtach and B. V. Parakhonskiy, Colloids Surf., A, 2022, 650, 129547.
283. J. Li, L. Van der Meeren, J. Verduijn, B. V. Parakhonskiy and A. G. Skirtach, Mater. Today Commun., 2022, 33, 104287.
284. M. S. Savelyeva, A. A. Abalymov, G. P. Lyubun, I. V. Vidyasheva, A. M. Yashchenok, T. E. L. Douglas, D. A. Gorin and B. V. Parakhonskiy, J. Biomed. Mater. Res., Part A, 2017, 105, 94–103.
285. H. Jiang and T. Kobayashi, Mater. Sci. Eng., C, 2017, 75, 478–486.
286. Y. Shao, H. Jia, T. Cao and D. Liu, Acc. Chem. Res., 2017, 50, 659–668.
287. M. P. Pileni, J. Phys. Chem. B, 2001, 105, 3358–3371.
288. C.-W. Wang, A. Oskooei, D. Sinton and M. G. Moffitt, Langmuir, 2010, 26, 716–723.
289. A. Saini, K. Theis-Bröhl, A. Koutsioubas, K. L. Krycka, J. A. Borchers and M. Wolff, Langmuir, 2021, 37, 4064–4071.
290. A. Khademhosseini and R. Langer, Nat. Protoc., 2016, 11, 1775–1781.
291. M. M. Stevens and J. H. George, Science, 2005, 310, 1135–1138.
292. N. W. Choi, M. Cabodi, B. Held, J. P. Gleghorn, L. J. Bonassar and A. D. Stroock, Nat. Mater., 2007, 6, 908–915.
293. J. J. Green and J. H. Elisseeff, Nature, 2016, 540, 386–394.
294. T. Dvir, B. P. Timko, D. S. Kohane and R. Langer, Nat. Nanotechnol., 2011, 6, 13–22.
295. D. Choi, J. Park, J. Heo, T. I. Oh, E. Lee and J. Hong, ACS Appl. Mater. Interfaces, 2017, 9, 12264–12271.
296. T. G. Kim, S.-H. Park, H. J. Chung, D.-Y. Yang and T. G. Park, J. Mater. Chem., 2010, 20, 8927.
297. J. Lee, V. Manoharan, L. Cheung, S. Lee, B.-H. Cha, P. Newman, R. Farzad, S. Mehrotra, K. Zhang, F. Khan, M. Ghaderi, Y.-D. Lin, S. Aftab, P. Mostafalu, M. Miscuglio, J. Li, B. B. Mandal, M. A. Hussain, K. Wan, X. S. Tang, A. Khademhosseini and S. R. Shin, ACS Nano, 2019, 13, 12525–12539.
298. A. Nishiguchi, H. Yoshida, M. Matsusaki and M. Akashi, Adv. Mater., 2011, 23, 3506–3510.
299. R. Ravichandran, J. R. Venugopal, S. Sundarrajan, S. Mukherjee and S. Ramakrishna, Biomaterials, 2012, 33, 846–855.
300. L. He, S. Tang, M. P. Prabhakaran, S. Liao, L. Tian, Y. Zhang, W. Xue and S. Ramakrishna, Macromol. Biosci., 2013, 13, 1601–1609.
301. Y. Luo, S. Wang, M. Shen, R. Qi, Y. Fang, R. Guo, H. Cai, X. Cao, H. Tomás, M. Zhu and X. Shi, Carbohydr. Polym., 2013, 91, 419–427.
302. K. Zhang, W. H. Chooi, S. Liu, J. S. Chin, A. Murray, D. Nizetic, D. Cheng and S. Y. Chew, Biomaterials, 2020, 256, 120225.
303. X. Zhang, Z. Li, X. Yuan, Z. Cui and X. Yang, Appl. Surf. Sci., 2013, 284, 732–737.
304. L.-Y. Cui, S.-C. Cheng, L.-X. Liang, J.-C. Zhang, S.-Q. Li, Z.-L. Wang and R.-C. Zeng, Bioact. Mater., 2020, 5, 153–163.
305. H.-D. Wu, J.-C. Yang, T. Tsai, D.-Y. Ji, W.-J. Chang, C.-C. Chen and S.-Y. Lee, Carbohydr. Polym., 2011, 85, 318–324.
306. B. Choi, S. Kim, B. Lin, B. M. Wu and M. Lee, ACS Appl. Mater. Interfaces, 2014, 6, 20110–20121.
307. X. Qi, T. Su, M. Zhang, X. Tong, W. Pan, Q. Zeng, Z. Zhou, L. Shen, X. He and J. Shen, ACS Appl. Mater. Interfaces, 2020, 12, 13256–13264.
308. S. Afewerki, A. Sheikhi, S. Kannan, S. Ahadian and A. Khademhosseini, Bioeng. Transl. Med., 2019, 4, 96–115.
309. D. M. Ryan and B. L. Nilsson, Polym. Chem., 2012, 3, 18–33.
310. L.-L. Li, G.-B. Qi, F. Yu, S.-J. Liu and H. Wang, Adv. Mater., 2015, 27, 3181–3188.
311. F. Yergoz, N. Hastar, C. E. Cimenci, A. D. Ozkan, T. Tekinay, M. O. Guler and A. B. Tekinay, Biomaterials, 2017, 134, 117–127.
312. A. Andukuri, W. P. Minor, M. Kushwaha, J. M. Anderson and H.-W. Jun, Nanomedicine, 2010, 6, 289–297.
313. J.-K. Kim, J. Anderson, H.-W. Jun, M. A. Repka and S. Jo, Mol. Pharm., 2009, 6, 978–985.
314. J. D. Hartgerink, E. Beniash and S. I. Stupp, Proc. Natl. Acad. Sci. U. S. A., 2002, 99, 5133–5138.
315. M. Rivas, L. del Valle, C. Alemán and J. Puiggalí, Gels, 2019, 5, 14.
316. N. Amosi, S. Zarzhitsky, E. Gilsohn, O. Salnikov, E. Monsonego-Ornan, R. Shahar and H. Rapaport, Acta Biomater., 2012, 8, 2466–2475.
317. A. M. Diez-Pascual and A. Rahdar, ChemMedChem, 2022, 17, e202200142.
318. K. Ariga, Y. M. Lvov, K. Kawakami, Q. Ji and J. P. Hill, Adv. Drug Delivery Rev., 2011, 63, 762–771.
319. B. Pilicheva, Y. Uzunova, I. Bodurov, A. Viraneva, G. Exner, S. Sotirov, T. Yovcheva and M. Marudova, J. Drug Delivery Sci. Technol., 2020, 59, 101897.
320. V. Albright, I. Zhuk, Y. Wang, V. Selin, B. van de Belt-Gritter, H. J. Busscher, H. C. van der Mei and S. A. Sukhishvili, Acta Biomater., 2017, 61, 66–74.
321. E. Redolfi Riva, A. Desii, S. Sartini, C. La Motta, B. Mazzolai and V. Mattoli, Langmuir, 2013, 29, 13190–13197.
322. V. Mohanta, G. Madras and S. Patil, ACS Appl. Mater. Interfaces, 2014, 6, 20093–20101 , https://pubs.acs.org/doi/10.1021/am505681e.
323. S. Türk and E. Yılmaz, J. Drug Delivery Sci. Technol., 2022, 67, 102943.
324. C. Du, J. Shi, J. Shi, L. Zhang and S. Cao, Mater. Sci. Eng., C, 2013, 33, 3745–3752.
325. J. Wang, H. Hao and J. H. Cai, J. Macromol. Sci., Part B: Phys., 2019, 58, 535–550.
326. J. Xing, Y. Cai, Y. Wang, H. Zheng and Y. Liu, Adv. Polym. Technol., 2020, 2020, 1–8.
327. N. M. Elbaz, A. Owen, S. Rannard and T. O. McDonald, Int. J. Pharm., 2020, 574, 118866.
328. S. Correa, N. Boehnke, E. Deiss-Yehiely and P. T. Hammond, ACS Nano, 2019, 13, 5623–5634.
329. Z. Li, D. Yuan, G. Jin, B. H. Tan and C. He, ACS Appl. Mater. Interfaces, 2016, 8, 1842–1853.
330. Y. Wang, V. Bansal, A. N. Zelikin and F. Caruso, Nano Lett., 2008, 8, 1741–1745.
331. N. Theodorakis, S.-F. Saravanou, N.-P. Kouli, Z. Iatridi and C. Tsitsilianis, Polymer, 2021, 13, 1228.
332. L. J. De Cock, S. De Koker, B. G. De Geest, J. Grooten, C. Vervaet, J. P. Remon, G. B. Sukhorukov and M. N. Antipina, Angew. Chem., Int. Ed., 2010, 49, 6954–6973.
333. J. Shao, M. Xuan, T. Si, L. Dai and Q. He, Nanoscale, 2015, 7, 19092–19098.
334. T. A. Debele, S. L. Mekuria and H.-C. Tsai, Mater. Sci. Eng., C, 2016, 68, 964–981.
335. L. Dai, T. Cheng, Y. Wang, H. Lu, S. Nie, H. He, C. Duan and Y. Ni, Cellulose, 2019, 26, 6891–6901.
336. N. Lin, A. Gèze, D. Wouessidjewe, J. Huang and A. Dufresne, ACS Appl. Mater. Interfaces, 2016, 8, 6880–6889.
337. Z. Li, H. Shim, M. O. Cho, I. S. Cho, J. H. Lee, S.-W. Kang, B. Kwon and K. M. Huh, Carbohydr. Polym., 2018, 184, 342–353.
338. B. P. Purcell, D. Lobb, M. B. Charati, S. M. Dorsey, R. J. Wade, K. N. Zellars, H. Doviak, S. Pettaway, C. B. Logdon, J. A. Shuman, P. D. Freels, J. H. Gorman III, R. C. Gorman, F. G. Spinale and J. A. Burdick, Nat. Mater., 2014, 13, 653–661.
339. G. E. Giammanco, C. T. Sosnofsky and A. D. Ostrowski, ACS Appl. Mater. Interfaces, 2015, 7, 3068–3076.
340. X. Ding, J. Gao, H. Awada and Y. Wang, J. Mater. Chem. B, 2016, 4, 1175–1185.
341. Y. Xie, J. Zhao, R. Huang, W. Qi, Y. Wang, R. Su and Z. He, Nanoscale Res. Lett., 2016, 11, 184.
342. S. Sutton, N. L. Campbell, A. I. Cooper, M. Kirkland, W. J. Frith and D. J. Adams, Langmuir, 2009, 25, 10285–10291.
343. A. Baral, S. Roy, A. Dehsorkhi, I. W. Hamley, S. Mohapatra, S. Ghosh and A. Banerjee, Langmuir, 2014, 30, 929–936.
344. H. Guo, G. Cui, J. Yang, C. Wang, J. Zhu, L. Zhang, J. Jiang and S. Shao, Biochem. Biophys. Res. Commun., 2012, 424, 105–111.
345. V. A. C. Puig-Sanvicens and C. E. Semino, Drug Delivery Transl. Res., 2013, 3, 330–335.
346. D. Ni, C. A. Ferreira, T. E. Barnhart, V. Quach, B. Yu, D. Jiang, W. Wei, H. Liu, J. W. Engle, P. Hu and W. Cai, J. Am. Chem. Soc., 2018, 140, 14971–14979.
347. R. Xiong, S. J. Soenen, K. Braeckmans and A. G. Skirtach, Theranostics, 2013, 3, 141–151.
348. E. Catanzaro, O. Feron, A. G. Skirtach and D. V. Krysko, Front. Immunol., 2022, 13, 925290.
349. L. Li, Z. Yang, S. Zhu, L. He, W. Fan, W. Tang, J. Zou, Z. Shen, M. Zhang, L. Tang, Y. Dai, G. Niu, S. Hu and X. Chen, Adv. Mater., 2019, 31, 1901187.
350. C. Xie, X. Zhen, Q. Lei, R. Ni and K. Pu, Adv. Funct. Mater., 2017, 27, 1605397.
351. D. Cui, J. Huang, X. Zhen, J. Li, Y. Jiang and K. Pu, Angew. Chem., 2019, 131, 5981–5985.
352. L. S. L. Janardhanam, V. V. Indukuri, P. Verma, A. C. Dusane and V. V. K. Venuganti, Mater. Sci. Eng., C, 2020, 115, 111118.
353. L. Van der Meeren, J. Verduijn, J. Li, E. Verwee, D. V. Krysko, B. V. Parakhonskiy and A. G. Skirtach, Appl. Surf. Sci. Adv., 2021, 5, 100111.
354. W. Ou, L. Jiang, R. K. Thapa, Z. C. Soe, K. Poudel, J.-H. Chang, S. K. Ku, H.-G. Choi, C. S. Yong and J. O. Kim, Theranostics, 2018, 8, 4574–4590.
355. O. Kreft, A. M. Javier, G. B. Sukhorukov and W. J. Parak, J. Mater. Chem., 2007, 17, 4471.
356. D. Zhu, L. Feng, N. Feliu, A. H. Guse and W. J. Parak, Adv. Mater., 2021, 33, 2008261.
357. L. I. Kazakova, L. I. Shabarchina, S. Anastasova, A. M. Pavlov, P. Vadgama, A. G. Skirtach and G. B. Sukhorukov, Anal. Bioanal. Chem., 2013, 405, 1559–1568.
358. L. Van der Meeren, J. Li, B. V. Parakhonskiy, D. V. Krysko and A. G. Skirtach, Anal. Bioanal. Chem., 2020, 412, 5015–5029.
359. S. Schmidt, P. A. L. Fernandes, B. G. De Geest, M. Delcea, A. G. Skirtach, H. Möhwald and A. Fery, Adv. Funct. Mater., 2011, 21, 1411–1418.
360. M. H. Bakker, C. C. S. Tseng, H. M. Keizer, P. R. Seevinck, H. M. Janssen, F. J. Van Slochteren, S. A. J. Chamuleau and P. Y. W. Dankers, Adv. Healthcare Mater., 2018, 7, 1701139.
361. J. I. Kim, B. S. Lee, C. Chun, J.-K. Cho, S.-Y. Kim and S.-C. Song, Biomaterials, 2012, 33, 2251–2259.
362. E. Lengert, A. M. Yashchenok, V. Atkin, A. Lapanje, D. A. Gorin, G. B. Sukhorukov and B. V. Parakhonskiy, RSC Adv., 2016, 6, 20447–20452.
363. E. Lengert, B. Parakhonskiy, D. Khalenkow, A. Zečić, M. Vangheel, J. M. Monje Moreno, B. P. Braeckman and A. G. Skirtach, Nanoscale, 2018, 10, 17249–17256.
364. X. Chen, Z. Liu, S. G. Parker, X. Zhang, J. J. Gooding, Y. Ru, Y. Liu and Y. Zhou, ACS Appl. Mater. Interfaces, 2016, 8, 15857–15863.
365. C. Wang, N. Zhao, Y. Huang, R. He, S. Xu and W. Yuan, Chem. Eng. J., 2020, 401, 126100.
366. K. N. Alagarsamy, S. Mathan, W. Yan, A. Rafieerad, S. Sekaran, H. Manego and S. Dhingra, Bioact. Mater., 2021, 6, 2261–2280.
367. A. La Porta, A. Sánchez-Iglesias, T. Altantzis, S. Bals, M. Grzelczak and L. M. Liz-Marzán, Nanoscale, 2015, 7, 10377–10381.
368. N. Bhattarai, J. Gunn and M. Zhang, Adv. Drug Delivery Rev., 2010, 62, 83–99.
369. K. Lv, Q. Li, L. Zhang, Y. Wang, Z. Zhong, J. Zhao, X. Lin, J. Wang, K. Zhu, C. Xiao, C. Ke, S. Zhong, X. Wu, J. Chen, H. Yu, W. Zhu, X. Li, B. Wang, R. Tang, J. Wang, J. Huang and X. Hu, Theranostics, 2019, 9, 7403–7416.
370. Z. Yang, G. Liang, L. Wang and B. Xu, J. Am. Chem. Soc., 2006, 128, 3038–3043.
371. K. Basu, A. Baral, S. Basak, A. Dehsorkhi, J. Nanda, D. Bhunia, S. Ghosh, V. Castelletto, I. W. Hamley and A. Banerjee, Chem. Commun., 2016, 52, 5045–5048.
372. W. Liu, H. Tang, L. Li, X. Wang, Z. Yu and J. Li, Cell Proliferation, 2021, 54, e13025.
373. R. Chang, Q. Zou, R. Xing and X. Yan, Adv. Ther., 2019, 2, 1900048.
374. H. Jin, G. Zhao, J. Hu, Q. Ren, K. Yang, C. Wan, A. Huang, P. Li, J.-P. Feng, J. Chen and Z. Zou, ACS Appl. Mater. Interfaces, 2017, 9, 25755–25766.
375. H. Xuan, X. Tang, Y. Zhu, J. Ling and Y. Yang, ACS Appl. Bio Mater., 2020, 3, 1628–1635.
376. F. Wang, J. Li, X. Tang, K. Huang and L. Chen, Colloids Surf., B, 2020, 190, 110925.
377. D. Cai, L. Shi, R. Long, G. Ren, S. Wang and Y. Liu, Carbohydr. Polym., 2021, 261, 117847.
378. A. R. Correia, I. Sampaio, E. J. Comparetti, N. C. S. Vieira and V. Zucolotto, Talanta, 2021, 233, 122506.
379. J. Fan, Y. Liu, S. Wang, Y. Liu, S. Li, R. Long, R. Zhang and R. K. Kankala, RSC Adv., 2017, 7, 32786–32794.
380. F. Zhang, C. Hu, Q. Kong, R. Luo and Y. Wang, ACS Appl. Mater. Interfaces, 2019, 11, 37147–37155.
381. S. Motamed, M. P. Del Borgo, K. Kulkarni, N. Habila, K. Zhou, P. Perlmutter, J. S. Forsythe and M. I. Aguilar, Soft Matter, 2016, 12, 2243–2246.
382. W. Nie, C. Peng, X. Zhou, L. Chen, W. Wang, Y. Zhang, P. X. Ma and C. He, Carbon, 2017, 116, 325–337.
383. K. Lalitha, Y. S. Prasad, C. U. Maheswari, V. Sridharan, G. John and S. Nagarajan, J. Mater. Chem. B, 2015, 3, 5560–5568.
384. Y. Hu, S. Hu, S. Zhang, S. Dong, J. Hu, L. Kang and X. Yang, Sci. Rep., 2021, 11, 9142.
385. J. Zheng, R. Fan, H. Wu, H. Yao, Y. Yan, J. Liu, L. Ran, Z. Sun, L. Yi, L. Dang, P. Gan, P. Zheng, T. Yang, Y. Zhang, T. Tang and Y. Wang, Nat. Commun., 2019, 10, 1604.
386. H. Wei, Z. Zhao, Y. Wang, J. Zou, Q. Lin and Y. Duan, ACS Appl. Mater. Interfaces, 2019, 11, 46479–46489.
387. M. Chang, M. Wang, Y. Chen, M. Shu, Y. Zhao, B. Ding, Z. Hou and J. Lin, Nanoscale, 2019, 11, 10129–10136.
388. K. Ariga, K. Minami, M. Ebara and J. Nakanishi, Polym. J., 2016, 48, 371–389.
389. J. Yamaguchi and K. Itami, Bull. Chem. Soc. Jpn., 2017, 90, 367–383.
390. L. Zhao, Q. Zou and X. Yan, Bull. Chem. Soc. Jpn., 2019, 92, 70–79.
391. P. Calandra, D. Caschera, V. Turco Liveri and D. Lombardo, Colloids Surf., A, 2015, 484, 164–183.
392. J. K. Scott and G. P. Smith, Science, 1990, 249, 386–390.
393. G. P. Smith, Science, 1985, 228, 1315–1317.
394. B. Pelaz, C. Alexiou, R. A. Alvarez-Puebla, F. Alves, A. M. Andrews, S. Ashraf, L. P. Balogh, L. Ballerini, A. Bestetti, C. Brendel, S. Bosi, M. Carril, W. C. W. Chan, C. Chen, X. Chen, X. Chen, Z. Cheng, D. Cui, J. Du, C. Dullin, A. Escudero, N. Feliu, M. Gao, M. George, Y. Gogotsi, A. Grünweller, Z. Gu, N. J. Halas, N. Hampp, R. K. Hartmann, M. C. Hersam, P. Hunziker, J. Jian, X. Jiang, P. Jungebluth, P. Kadhiresan, K. Kataoka, A. Khademhosseini, J. Kopeček, N. A. Kotov, H. F. Krug, D. S. Lee, C.-M. Lehr, K. W. Leong, X.-J. Liang, M. Ling Lim, L. M. Liz-Marzán, X. Ma, P. Macchiarini, H. Meng, H. Möhwald, P. Mulvaney, A. E. Nel, S. Nie, P. Nordlander, T. Okano, J. Oliveira, T. H. Park, R. M. Penner, M. Prato, V. Puntes, V. M. Rotello, A. Samarakoon, R. E. Schaak, Y. Shen, S. Sjöqvist, A. G. Skirtach, M. G. Soliman, M. M. Stevens, H.-W. Sung, B. Z. Tang, R. Tietze, B. N. Udugama, J. S. VanEpps, T. Weil, P. S. Weiss, I. Willner, Y. Wu, L. Yang, Z. Yue, Q. Zhang, Q. Zhang, X.-E. Zhang, Y. Zhao, X. Zhou and W. J. Parak, ACS Nano, 2017, 11, 2313–2381.

---