Self-Assembled Multiple-Enzyme Composites for Enhanced Synergistic Cancer Starving-Catalytic Therapy

Inspired by the particularity of tumor microenvironments, including acidity and sensibility to reactive oxygen species (ROS), advanced and smart responsive nanomaterials have recently been developed. The present study synthesized tumor-targeted and pH-sensitive supramolecular micelles that self-assembled via host-guest recognition. The micelles consumed intratumoral glucose and lactate via loading with glucose oxidase (GOD) and lactate oxidase (LOD). Intratumoral glucose and lactate were converted into hydrogen peroxide (H₂O₂) and were sequentially reduced to highly toxic hydroxyl radicals (^•OH) via the peroxidase (POD)-like activity of the loaded C-dot nanozymes. Tumor-killing effects were observed via cascade catalytic reactions. After an intravenous injection, the nanocomposite exhibited an excellent tumor-targeted ability with good biocompatibility, which demonstrated its effective antitumor effect. The nanocomposite effectively combined starvation and catalytic therapies and exerted a synergistic anticancer effect with minimal side effects and without external addition.