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.
Keywords: copper peroxide nanodots; copper sulfide nanoassemblies; photoresponsive agents; proteins; reactive oxygen species; wound infection.