Core@paratroopers Nanoassemblies with Catalytic Cascade for Efficient Tumor Starvation Therapy

The catalytic therapy based on the nanozymes has received increasing interest in cancer treatment. However, the catalytic capabilities of standalone nanozymes are relatively limited, necessitating the development of a nano-bio composite system that integrates both nanozymes and natural enzymes. This construction often inevitably leads to interference between natural enzyme and nanozymes, resulting in reduced synergistic performance. Herein, a cascade catalysis system featuring the "core@paratroopers" structure is proposed, wherein hollow manganese dioxide (HMnO2) serves as "core" and ultra-small hybrid single-micelle (H-micelle) encapsulated with glucose oxidase (GOx) as "paratroopers" (H-micelle-GOx). The outer SiO2 layer of the H-micelle can effectively protect the GOx. Under hypoxic conditions, HMnO2 reacts with endogenous H2O2 to produce O-2, thereby enhancing the catalytic efficiency of GOx for starvation therapy. Simultaneously, the generated H2O2 boosts the catalytic efficiency of HMnO2, accelerating local O-2 generation and alleviating tumor hypoxia. Additionally, this system exhibits rapid degradation in the tumor microenvironment characterized by high glutathione (GSH) expression, facilitating the release and deep penetration of the ultra-small H-micelle-GOx "paratroopers" within the solid tumor.