Trienzyme-integrated gold nanoflowers with high-efficiency enzyme cascades for synergistic multimodal nanocatalytic therapy

The design of versatile nanoplatforms with synergistic effects for targeted tumor therapy, has always been both a desire and a challenge. This study reports an actively hybrid nanoplatform (AuNFs-GCH@CM) that combines photothermal therapy with enzyme cascade catalysis for multimodal cancer synergistic therapy. The system is designed around gold nanoflowers loaded sequentially with various natural active enzymes, including glucose oxidase (GOx), catalase (CAT), and horseradish peroxidase (HRP), and then cover the surface of AuNFs-GCH with 4T1 tumor cell membrane (CM). CAT provides oxygen for GOx in the hypoxic tumor microenvironment (TME), while HRP catalyzes the removal of GOx products, achieving efficient glucose depletion and hydroxyl radical generation in tumors, thereby enabling enzymatic therapy, starvation therapy, and chemodynamic therapy (CDT). Moreover, local hyperthermia (PTT) can promote the catalytic efficiency of the cascade enzymes, further enhancing ROS effects and achieving an extremely high antitumor effect. Therefore, the in vivo and in vitro results validate our design，AuNFs-GCH@CM synergistic therapy effectively inhibits tumor growth with low cytotoxicity, high targeting, and biocompatibility, exhibiting great potential for multi-enzyme cascade and multimodal tumor therapy.