Copper Sulfide Nanoassemblies for Catalytic and Photoresponsive Eradication of Bacteria from Infected Wounds

Bovine serum albumin (BSA)-encapsulated copper sulfide nanocrystals (CuS NCs) were prepared by heating an alkaline solution containing copper ions and BSA without an additional sulfur source. At a high BSA concentration (0.8 mM), nanoassembly of the as-formed CuS NCs occurs to form BSA–CuS NCs as a result of the formation of BSA gel-like structures. In addition to their intrinsic photothermal properties, the BSA–CuS NCs possess rich surface vacancies and thus exhibit enzyme-like and photodynamic activities. Spontaneous generation of hydrogen peroxide (H₂O₂) led to the in situ formation of copper peroxide (CPO) nanodots on the BSA–CuS NCs to catalyze singlet oxygen radical generation. The antimicrobial response was enhanced by >60-fold upon NIR laser irradiation, which was ascribed to the combined effect of the photodynamic and photothermal inactivation of bacteria. Furthermore, BSA–CuS NCs were transdermally administered onto a methicillin-resistant Staphylococcus aureus-infected wound and eradicated >99% of bacteria in just 1 min under NIR illumination due to the additional peroxidase-like activity of BSA–CuS NCs, transforming H₂O₂ at the infection site into hydroxyl radicals and thus increasing the synergistic effect from photodynamic and photothermal treatment. The BSA–CuS NCs exhibited insignificant in vitro cytotoxicity and hemolysis and thus can serve as highly biocompatible bactericides in preclinical applications to effectively eradicate bacteria.