期刊
CHEMICAL SCIENCE
卷 13, 期 29, 页码 8657-8666出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d2sc02488h
关键词
-
资金
- National Natural Science Foundation of China (NNSFC) [21874012]
- National Key Research and Development Program of China [2019YFC1805600]
- NNSFC [21974010]
In this study, supramolecular nanomaterials were used to efficiently load and release siRNA with precise and monitorable site-specificity. The strategy of constructing these materials using modular and hierarchical self-assembly allowed for effective delivery and tumor inhibition. This study expands the application of supramolecular nanomaterials in diagnosis and treatment.
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 superset of 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 superset of G-siRNA was constructed via comprehensive weak interactions including electrostatic, hydrophobic-hydrophilic, host-guest and pi-pi 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 superset of 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.
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