Photothermal-reinforced and glutathione-triggered in Situ cascaded nanocatalytic therapy.

Tumor microenvironment (TME)-responsive nanoformulations that catalyze a cascade of intracellular redox reactions showed promise for tumor treatment with high specificity and efficiency. In this study, we report Cu-doped zeolitic imidazolate frameworks-coated polydopamine nanoparticles (PDA@Cu/ZIF-8 NPs) for glutathione-triggered and photothermal-reinforced sequential catalytic therapy against breast cancer. In the TME, the PDA@Cu/ZIF-8 NPs could initially react with antioxidant glutathione (GSH), inducing GSH depletion and Cu generation. Whereafter, the generated Cu would catalyze local HO to produce highly toxic hydroxyl radicals (·OH) through an efficient Fenton-like reaction even in weakly acidity. Importantly, the PDA could exert excellent photothermal conversion effect to simultaneously accelerate GSH consumption and improve the Fenton-like reaction for further expanding the intracellular oxidative stress, which innovatively achieves a synergistic photothermal-chemodynamic therapy for highly efficient anticancer treatment.