Hypoxia-Activated and Light-Amplified Paclitaxel Release for Potentiated Photodynamic and Chemotherapy

Iridium(III) complexes exhibit strong phosphorescence, tunable emission, and spatiotemporally controlled light-activation properties, making them ideal candidates for photodynamic therapy (PDT). Herein, self-amplified nanoparticles combining polycarbonate-iridium(III) conjugates (PC-Ir) and hypoxia-responsive paclitaxel prodrugs (PTX₂-Azo) were engineered. Upon 660 nm laser irradiation, PC-Ir generates substantial reactive oxygen species (ROS) via both type I and type II photodynamic pathways. Simultaneously, the consumption of localized oxygen by PDT exacerbates hypoxia, therefore promoting the release of potent paclitaxel (PTX) from azobenzene-linked PTX and releasing CO₂, which generates mechanical force to accelerate the escape of nanoparticles to the cytoplasm. This prodrug strategy not only suppresses premature drug leakage, improves the poor stability of PTX, and minimizes off-target effects but also integrates light-activated PDT and PDT-accelerated chemotherapy to provide precision cancer therapy.