Nature-inspired cell membrane-coated artificial biocatalysts with Os-single-atom sites and multienzyme-mimetic activities for targeted tumor therapy

Constructing highly efficient and specific artificial biocatalysts with multi-enzyme activities for generating reactive oxygen species (ROS) is extremely desirable but remains challenging for targeted malignant melanoma (MM) therapy. Here, inspired by the high-efficient and specificity of natural enzymes, an innovative cancer cell membrane (CCM) coated and multi-enzyme biocatalyst (OsCu-O_v@CCM) with single atom Os catalytic centers and oxygen vacancies (O_v) for targeted MM therapy is reported. Owing to the excellent electronic properties of Os active sites and structure diversities, the synthesized biocatalyst (OsCu-O_v) exhibits exceptional ROS-catalytic activities, including peroxidase (POD)-, halogen peroxidase (HPO)- and catalase (CAT)-mimetic behaviors. CCM coating with excellent biological interface properties including homologous targeting, efficient OsCu-O_v delivery. Consequently, the vivo experiments reveal that the OsCu-O_v@CCM can provide high-efficiency therapeutic efficacy for MM by the production of ROS and remission of tumor hypoxic microenvironment (THME), meanwhile, it induces to mitochondrial damage, thereby activating the Bax-Bcl-2-Caspase 3 axis, which further initiates apoptosis. It is suggested that the design of this artificial biocatalyst with CCM coated Os-single-atom sites will offers a new guidance for developing high-performance ROS-catalytic materials in tumor therapy and other ROS-related diseases.