Synthesis and pH-responsive properties of bacteria mimicking hydrogel capsules

Abstract

The evolution of a non-spherical shape of microorganisms helped them survive by evading capture and digestion, which is crucial for their biological functioning. Synthetic imitation of the non-spherical shapes of various microorganisms and cells can enhance the ability of synthetic particulates to deliver therapeutics inside the body. Herein, we synthesized non-spherical polymer hydrogel microcapsules with bacteria-mimicking shapes, including prolate ellipsoid, peanut, and hourglass shapes similar to some pathogen microorganisms like Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Corynebacterium diphtheriae. The hydrogel shells were synthesized through a multilayer assembly of hydrogen-bonded poly(methacrylic acid) (PMAA) and non-ionic poly(N-vinylpyrrolidone) (PVPON) homopolymers on the surfaces of non-porous iron oxide microparticles of 2 μm in length. After covalent cross-linking of PMAA layers, followed by the release of PVPON at pH = 8 and the dissolution of the particle templates, curved rod-shaped (PMAA) multilayer hydrogel microcapsules with a pH-responsive shell were obtained. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis confirmed the covalent cross-linking of the shell and the release of PVPON from the capsule shell networks. The (PMAA) hydrogel capsules demonstrated excellent retention of their ellipsoid, peanut, and hourglass shapes after core dissolution in acidic solutions despite a nanothin (∼40 nm) hydrogel membrane. Remarkably, all systems retained bacteria-like shapes in solutions at pH = 8, increasing in size by 20–30%, as confirmed by confocal fluorescence microscopy. All bacteria-like shaped microcapsules demonstrated homogeneous swelling in all directions regardless of the coating location at the initial particle perimeter, indicating similar cross-linking for all shapes and no effect of the iron oxide particle surfaces on the formation of the hydrogel shell. This work can help develop polymeric non-spherical particulates that are adaptable and on-demand for biomedical applications, including advanced targeting of pathological tissues and developing artificial cells with intelligent responses to environmental cues. Synthetic imitation of bacteria-like shapes and morphological flexibility demonstrated in this work using a multilayer assembly of polymer hydrogel capsules can bring new insights into the understanding and synthetic reproduction of properties essential for the synthetic particulates to evade the immune system and increase tissue targeting. These properties can be critical for developing unconventional particulates for controlled delivery and advanced imaging.