Nanocatalyst with Self-Strengthening Cascade Reaction for Enhanced Cancer Therapy

Nanocatalysts with extraordinary activity have attracted extensive research interest and great potential in tumor therapy. However, the widely explored Cu-based copper sulfide-enabled cancer therapy suffers from limited catalytic efficiency. This is primarily attributed to the susceptibility of single-phase nanocrystalline catalysts to complexation within the homogeneous catalyst and the complex tumor microenvironment (TME). Developing nanocatalysts with a broad energy band and high oxidative as well as reductive capacities remains a significant challenge. Herein, we first constructed a heterojunction (HJ)-based nanophotocatalytic platform, denoted as Cu₇S₄-In₂S₃@GOx@PEG, CIGP, wherein glucose oxidase (GOx) and poly(ethylene glycol) were modified on the Cu₇S₄-In₂S₃ HJs. The developed CIGP showed excellent phototriggered reactive oxygen species (ROS) generation ability via reaction with O₂ and H₂O₂, owing to the Cu₇S₄-In₂S₃ HJs, in which the spatial separation dynamics of photogenerated electrons-holes was improved. In addition, the modified GOx of CIGP can catalyze the conversion of glucose into hydrogen peroxide (H₂O₂) and gluconic acid, thereby regulating the pH of the TME and altering the redox dynamic balance to favor ROS accumulation. Under irradiation, CIGP inhibited the growth of tumor cells by spatiotemporal controllable photothermal therapy. Taken together, CIGP provided an innovative paradigm for remodeling the acidity of the TME and synergistically enhancing the antitumor response.