Cu/Au-doped nanopolymers with multiple catalytic activities for NIR II laser-promoted nanocatalytic tumor therapy

Breast cancer remains a significant global health concern owing to the limitations of conventional therapies, such as side effects, drug resistance, and high costs. Nanocatalytic therapy has emerged as a promising alternative due to its tumor specificity, spatiotemporal controllability, and noninvasiveness. However, its effectiveness is limited by endogenous antioxidants like glutathione (GSH) and the low catalytic activity of nanocatalysts. Herein, an Cu/Au-doped polypyrrole nanocatalyst, Cu-AuPP, with multiple catalytic activities is developed by sequentially polymerizing pyrrole monomers using CuCl₂ and HAuCl₄, followed by PEGylation. The obtained Cu-AuPP catalyzes the production of hydroxyl radicals (·OH) and facilitates the oxidation of GSH to GSSG via redox reactions mediated by multivalent Cu ions, leading to oxidative damage, mitochondrial dysfunction, and tumor cell apoptosis. Upon 1064 nm laser irradiation, these catalytic activities were enhanced by elevated temperature and electron-hole separation mediated by Au nanoclusters, resulting in more intense oxidative damage to tumor cells. Collectively, the developed Cu-AuPP nanocatalytic medicine capable of simultaneously catalyzing GSH depletion and ·OH production via several improved catalytic mechanisms, has significant promise for the treatment of malignant tumors.