Bimetallic PtPd Atomic Clusters as Apoptosis/Ferroptosis Inducers for Antineoplastic Therapy through Heterogeneous Catalytic Processes

Active polymetallic atomic clusters can initiate heterogeneous catalytic reactions in the tumor microenvironment, and the products tend to cause manifold damage to cell metabolic functions. Herein, bimetallic PtPd atomic clusters (BAC) are constructed by the stripping of Pt and Pd nanoparticles on nitrogen-doped carbon and follow-up surface PEGylation, aiming at efficacious antineoplastic therapy through heterogeneous catalytic processes. After endocytosed by tumor cells, BAC with catalase-mimic activity can facilitate the decomposition of endogenous H₂O₂ into O₂. The local oxygenation not only alleviates hypoxia to reduce the invasion ability of cancer cells but also enhances the yield of ^•O₂^– from O₂ catalyzed by BAC. Meanwhile, BAC also exhibit peroxidase-mimic activity for ^•OH production from H₂O₂. The enrichment of reactive oxygen species (ROS), including the radicals of ^•OH and ^•O₂^–, causes significant oxidative cellular damage and triggers severe apoptosis. In another aspect, intrinsic glutathione (GSH) peroxidase-like activity of BAC can indirectly upregulate the level of lipid peroxides and promote ferroptosis. Such deleterious redox dyshomeostasis caused by ROS accumulation and GSH consumption also results in immunogenic cell death to stimulate antitumor immunity for metastasis suppression. Collectively, this paradigm is expected to inspire more facile designs of polymetallic atomic clusters in disease therapy.