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

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, PPNP(siRNA)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 PPNP(siRNA)disassociation. Based on these innovative features, excellent synergistic therapeutic efficacy of chemo- and RNAi therapies of PPNP(siBcl-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.