A Photo-Activated H2 Nanogenerator for Enhanced Chemotherapy of Bladder Cancer

Hydrogen gas can mitigate oxidative stress in many diseases that is regarded to be safe and free of side effect. Inspired by a metalloenzyme in a variety of microorganisms, here we propose a photo-activated H2 nanogenerator that comprises a fluorinated chitosan (FCS), a chemotherapeutic drug (Gemcitabine, GEM), and a catalyst of H2 production ([FeFe]TPP) that can form self-assembled [FeFe]TPP/GEM/FCS nanoparticles (NPs). The [FeFe]TPP/GEM/FCS NPs exhibit excellent transmucosal and tumor cell penetration capacities after intravesical instillation into the bladder, and can efficiently produce H2 gas in situ upon a 660 nm laser irradiation, which significantly enhances the efficacy of hydrogen-chemotherapy of cancer in vitro and in vivo. Moreover, we discover that H2 gas in hydrogen-chemotherapy can inhibit mitochondrial function, hinder ATP synthesis, and cause the reduction of P-gp efflux pump function, which finally attenuate P-gp protein drug transport capacity in cancer cells. This photo-activated H2 evolution in situ to improve the therapeutic efficacy of chemotherapy of bladder cancer may present an effective hydrogen-chemotherapy strategy for cancer treatment.