H2O2 Self‐Producing Single‐Atom Nanozyme Hydrogels as Light‐Controlled Oxidative Stress Amplifier for Enhanced Synergistic Therapy by Transforming “Cold” Tumors

Single‐atom nanozyme (SAzyme) with peroxidase‐like activity can alter cellular redox balance and shows promising potential for tumor therapy. However, the “cold” immune microenvironment and limited amount of hydrogen peroxide (H2O2) in solid tumors severely restrict its efficacy. Herein, a light‐controlled oxidative stress amplifier system is designed by co‐encapsulating Pd‐C SAzymes and camptothecin in agarose hydrogel, which exhibits enhanced synergistic antitumor activity by self‐producing H2O2 and transforming “cold” tumors. In this nanozyme hydrogel system, the Pd‐C SAzyme converts near‐infrared laser into heat, resulting in agarose degradation and consequent camptothecin release. The camptothecin increases H2O2 level in tumors by activating nicotinamide adenine dinucleotide phosphate oxidase, improving the catalytic performance of SAzymes with peroxidase‐like activity. Moreover, the combination of photothermal therapy, chemotherapy, and nanozyme‐based catalytic therapy further facilitates tumor immunogenic death and enhanced antitumor immunity. The results reveal the synergistic antitumor potential of the novel SAzyme/chemotherapeutics‐based hydrogel system. In this article, the authors design a light‐controlled oxidative stress amplifier system by co‐encapsulating Pd‐C single atom nanozyme and camptothecin in agarose hydrogel, which exhibits enhanced synergistic antitumor activity through self‐producing H2O2 and transforming “cold” tumors.