Cancer Cell Membrane Biomimetic Mesoporous Nanozyme System with Efficient ROS Generation for Antitumor Chemoresistance.

Single-atom nanozymes (SAZs) with reaction specificity and optimized catalytic properties have great application prospects in tumor therapy. But the complex tumor microenvironment (low content of H2O2) limits its therapeutic effect. In this study, we developed a bionic mesoporous Fe SAZs/DDP nanosystem (CSD) for enhanced nanocatalytic therapy (NCT)/chemotherapy by simultaneously encapsulating the chemotherapeutic drugs cisplatin (DDP) and Fe SAZs with high peroxidase (POD) activity into the cancer cell membrane. CSD could evade immune recognition and actively targets tumor sites, and DDP upregulates endogenous H2O2 levels by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, thereby enhancing SAZs-mediated hydroxyl radical (·OH) production, which subsequently leads to mitochondrial damage and intolerance to chemotherapy drug. We used the HGC27/DDP cell line for in vitro and in vivo experiments. The results showed that CSD achieved good therapeutic benefits, without any side effects such as inflammatory reaction. This system can induce multiple antitumor effect with H2O2 self-supply, mitochondrial damage, and ATP downregulation and eventually lead to chemosensitization.