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Photomediated Reactive Oxygen Species‐Generable Nanoparticles for Triggered Release and Endo/Lysosomal Escape of Drug upon Attenuated Single Light Irradiation

Nanoparticles with “smart” stimuli‐responsive materials and multiple therapeutic strategies in a single delivery platform have emerged for highly efficient cancer therapy. Here, photomediated reactive oxygen species (ROS)‐generable nanoparticles are designed that can trigger drug release and endo/lysosomal escape upon attenuated single light irradiation, simultaneously, for synergistic chemo‐photodynamic ablation. In this study, the self‐ROS‐generable nanoparticles (SRNs) are prepared from the polymer based on polysaccharide, chlorin e6 as ROS generator and lipoic acid as ROS scavenger covalently conjugated pullulan with anticancer drug (doxorubicin, DOX) through self‐assembly, and can disassemble via the ROS‐mediated reduction of lipoyl group in response to low level exogenous single light switch. After cellular internalization in hepatic cancer through asialoglycoprotein receptor (ASGPR, as pullulan receptor)‐mediated endocytosis, once irradiated, SRNs are able to produce ROS that can simultaneously induce drug release triggering and endo/lysosomal escape of DOX into cytoplasm as well as directly photodynamic therapy for highly efficient chemo‐photodynamic cancer therapy. This promising delivery system, which has huge potential in biomedical applications, may be optimal for smart delivery platform.