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Photoactivated polyprodrug nanoparticles for effective light-controlled Pt(iv) and siRNA codelivery to achieve synergistic cancer therapy

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Abstract

Endo/lysosomal escape and the subsequent controllable/precise release of drugs and genes are key challenges for efficient synergistic cancer therapy. Herein, we report a photoactivated polyprodrug nanoparticle system (PPNPsiRNA) centered on effective light-controlled codelivery of Pt(IV) prodrug and siRNA for synergistic cancer therapy. Under green-light irradiation, PPNPsiRNA can sustainedly generate oxygen-independent azidyl radicals to facilitate endo/lysosomal escape through the photochemical internalization (PCI) mechanism. Besides, concurrent Pt(II) release and siRNA unpacking could occur in a controllable manner after the decomposition of Pt(IV), main chain shattering of photoactivated polyprodrug and the PPNPsiRNA disassociation. Based on these innovative features, excellent synergistic therapeutic efficacy of chemo- and RNAi therapies of PPNPsiBcl-2 could be achieved on ovarian cancer cells under light irradiation. The facile synthesized and prepared photoactivatable polyprodrug nanoparticle system provides a new strategy for effective gene/drug codelivery, where controllable endo/lysosomal escape and the subsequent drug/gene release/unpacking play vital roles, which could be adopted as a versatile codelivery nanoplatform for the treatment of various cancers.

Graphical abstract: Photoactivated polyprodrug nanoparticles for effective light-controlled Pt(iv) and siRNA codelivery to achieve synergistic cancer therapy

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Supplementary files

Article information


Submitted
27 Apr 2020
Accepted
26 May 2020
First published
28 May 2020

J. Mater. Chem. B, 2020, Advance Article
Article type
Paper

Photoactivated polyprodrug nanoparticles for effective light-controlled Pt(IV) and siRNA codelivery to achieve synergistic cancer therapy

Q. Zhang, G. Kuang, D. Zhou, Y. Qi, M. Wang, X. Li and Y. Huang, J. Mater. Chem. B, 2020, Advance Article , DOI: 10.1039/D0TB01103G

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