Entropy-driven nanoparticles possess abundant active sites and unique electronic structures, giving them higher catalytic efficiency and selectivity, making them promising for catalytic tumor therapy. However, medium-entropy nanozymes (MEzymes) are hindered by their intrinsic thermodynamic instability. This paper introduces a homologous cancer cell membrane-coated ultra-small medium-entropy nanozyme system (MEzyme@HCCM) for catalysis in targeted ROS-mediated tumor therapy.This enzyme is produced through a universal metal-ligand crosslinking strategy, creating simple and scalable complexes of metal ions and ligand molecules. In vitro results show that RuPtIrMo MEzyme@HCCM exhibits excellent peroxidase-like activity. In addition, it can target and deliver to tumor cells by recognizing homologous target proteins in tumor cells, thereby enhancing the tumor cell killing efficacy. In vivo results indicate that MEzyme@HCCM can rapidly catalyze endogenous hydrogen peroxide to produce highly toxic hydroxyl radicals.This resulted in over 60% inhibition of tumor growth. Proteomics analysis provided in-depth insights into ROS-mediated pathways, including DNA damage, tumor proliferation suppression, apoptosis, and autophagy. This work establishes a new perspective on enzyme preparation and simultaneously pioneers its biomedical applications.

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https://www.x-mol.com/paper/1990134285322006528/t?adv