Issue 29, 2022

Modular and hierarchical self-assembly of siRNAs into supramolecular nanomaterials for soft and homogeneous siRNA loading and precise and visualized intracellular delivery

Abstract

siRNA therapeutics are challenged by homogeneous and efficient loading, maintenance of biological activities, and precise, dynamic and monitorable site-release. Herein, supramolecular nanomaterials of WP5⊃G–siRNA were constructed by modular and hierarchical self-assembly of siRNA with guest (3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione derivative, G) and host (pillar[5]arene, WP5) molecules in the same system. Demonstrated by experiments and theoretical calculations, WP5⊃G–siRNA was constructed via comprehensive weak interactions including electrostatic, hydrophobic–hydrophilic, host–guest and π–π interactions. Therefore, siRNAs were efficiently loaded, maintaining good stability, bioactivities and biocompatibilities. At pH 6.8, G was protonated to give weak acidic-responsive “turn-on” fluorescent signals, which realized the precise location of cancer sites. This triggered a subsequent delivery and a dynamic release of siRNA in cancer cells under acidic conditions for the entire collapse of WP5⊃G–siRNA by the protonation of both WP5 and G. By both in vitro and in vivo experiments, precise and visualized delivery to cancer sites was achieved to exhibit effective tumour inhibition. This provided an efficient and soft strategy of siRNA therapies and expanded the application of supramolecular nanomaterials in diagnosis and treatment.

Graphical abstract: Modular and hierarchical self-assembly of siRNAs into supramolecular nanomaterials for soft and homogeneous siRNA loading and precise and visualized intracellular delivery

Supplementary files

Article information

Article type
Edge Article
Submitted
04 May 2022
Accepted
02 Jul 2022
First published
05 Jul 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 8657-8666

Modular and hierarchical self-assembly of siRNAs into supramolecular nanomaterials for soft and homogeneous siRNA loading and precise and visualized intracellular delivery

X. Guan, F. Meng, H. Tan, X. Wang, J. Li, J. Wei, J. Ouyang and N. Na, Chem. Sci., 2022, 13, 8657 DOI: 10.1039/D2SC02488H

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