Chemodynamic
therapy (CDT) has emerged as a promising strategy for
tumor treatment. Nevertheless, the low Fenton catalytic efficiency and the high concentration of
glutathione (GSH) in
cancer cells largely decline antitumor efficacy of CDT. To self-augment antitumor effect of the CDT by combining with
photothermal therapy (PTT), the unique photothermal nanozymes that doubly depleted GSH, and generated massive
hydroxyl radicals (·OH) in the
hyperthermia/acidity-activated manner were developed. Through the coordination of Fe3+
ions with PEGylated
chitosan (PEG-CS)-modified
polydopamine (PDA) nanoparticles, the attained Fe3+@PEG-CS/PDA nanozymes showed outstanding colloidal stability, photothermal conversion efficiency and acidity-triggered Fe3+ release. By GSH-mediated valence states transition of Fe3+
ions and Michael reaction between GSH and
quinone-rich PDA, the nanozymes sufficiently executed dual depletion of GSH with the elevated temperature.Under mimic
tumor acidity and near-infrared (NIR) irradiation condition, the endocytosed nanozymes effectively converted intracellular H2O2 into toxic ·OH upon amplified Fenton reaction, thereby potently killing 4T1
cancer cells and RAW 264.7 cells. Importantly, the nanozymes prominently suppressed 4T1
tumor growth in vivo and
metastasis of
cancer cells by CDT/PTT combination
therapy without significant systemic toxicity. Our study provides novel visions in design of therapeutic nanozymes with great clinical translational prospect for
tumor treatment.