Photoactivatable Prodrug-Backboned Polymeric Nanoparticles for Efficient Light-Controlled Gene Delivery and Synergistic Treatment of Platinum-Resistant Ovarian Cancer

摘要： Combination of chemotherapy and gene therapy provides an effective strategy for cancer treatment. However, lacking of suitable co-delivery systems with efficient endo/lysosomal escape and controllable drug release/gene unpacking is the major bottleneck for maximizing the combinational therapeutic efficacy. Herein, we developed a photoactivatable Pt(IV) prodrug-backboned polymeric nanoparticles system (CNPPtCP/si(c-fos)) for light-controlled si(c-fos) delivery and synergistic photoactivated chemotherapy (PACT) and RNAi on platinum-resistant ovarian cancer (PROC). Upon blue light irradiation (430 nm), CNPPtCP/si(c-fos) could generate oxygen-independent N3? with mild oxidation energy for efficient endo/lysosomal escape through N3?-assisted photochemical internalization with less gene deactivation. Thereafter, along with Pt(IV) prodrug activation, CNPPtCP/si(c-fos) would be disassociated to release active Pt(II) and unpack si(c-fos) simultaneously. Both in vitro and in vivo results demonstrated that CNPPtCP/si(c-fos) displayed excellent synergistic therapeutic efficacy on PROC with low toxicity. This PACT prodrug-backboned polymeric nanoplatform may provide a promising gene/drug co-delivery tactics for treatment of various hard-to-tackle cancers.