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Green Tea Catechin Dramatically Promotes RNAi Mediated by Low-Molecular-Weight Polymers.
ACS Central Science 2018 October 25
Cytosolic delivery is the major challenge that limits the clinical translation of siRNA-based therapeutics. Although thousands of polymers have been developed for siRNA delivery, the efficiency-toxicity correlation is unsatisfactory. Here, we report a facile strategy to fabricate core-shell-structured nanoparticles with robust siRNA delivery efficiency. The nanoparticle is prepared by entropy-driven complexation of siRNA with a green tea catechin to yield a negatively charged core, followed by coating low-molecular-weight polymers to form the shell. This supramolecular strategy facilitates the polymers condensing siRNA into uniform nanoparticles. The nanoparticle specifically down-regulates target genes in vitro and in vivo , and efficiently attenuates chronic intestinal inflammation in an inflammatory bowel disease model. Notably, the highly efficient nanoparticles are applicable for various polymers with different topologies and chemical compositions, providing a versatile technique to break down the efficiency-toxicity correlation of cationic polymers. The proposed strategy in this study permits the development of a promising platform for polymer-mediated siRNA delivery.
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