Confining Prepared Ultrasmall Nanozymes Loading ATO for Lung Cancer Catalytic Therapy/Immunotherapy

Abstract Nanozymes with inherent enzyme‐mimicking catalytic properties combat malignant tumor progression via catalytic therapy, while the therapeutic efficacy still needs to be improved. In this work, ultrasmall platinum nanozymes (nPt) in a confined domain of a wormlike pore channel in gold nanobipyramidal–mesoporous silica dioxide nanocomposites, producing nanozyme carriers AP‐mSi with photoenhanced peroxidase ability, are innovatively synthesized. Afterward, based on the prepared AP‐mSi, a lung‐cancer nanozymes probe (AP‐HAI) is ingeniously produced by removing the SiO₂ template, modifying human serum albumin, and loading atovaquone molecules (ATO) as well as IR780. Under NIR light irradiation, inner AuP and IR780 collaborate for photothermal process, thus facilitating the peroxidase‐like catalytic process of H₂O₂. Additionally, loaded ATO, a cell respiration inhibitor, can impair tumor respiration metabolism and cause oxygen retention, hence enhancing IR780's photodynamic therapy (PDT) effectiveness. As a result, IR780's PDT and nPt nanozymes' photoenhanced peroxidase‐like ability endow probes a high ROS productivity, eliciting antitumor immune responses to destroy tumor tissue. Systematic studies reveal that the obvious reactive oxygen species (ROS) generation is obtained by the strategy of using nPt nanozymes and reducing oxygen consumption by ATO, which in turn enables lung‐cancer synergetic catalytic therapy/immunogenic‐cell‐death‐based immunotherapy. The results of this work would provide theoretical justification for the practical use of photoenhanced nanozyme probes.