Surface-charge-switch triggered self assembly of vancomycin modified carbon nanodots for enhanced photothermal eradication of vancomycin-resistant Enterococci biofilms

A new type of vancomycin (Van)-modified carbon nanodots (CNDs@Van) with pH-responsive surface charge switchable activity was successfully developed by covalently cross-linking Van on the surface of carbon nanodots (CNDs). Polymeric Van was formed on the surface of CNDs by covalent modification, which enhanced the targeted binding of CNDs@Van to vancomycin-resistant enterococci (VRE) biofilms and effectively reduced the carboxyl groups on the surface of CNDs to achieve pH-responsive surface charge switching. Most importantly, CNDs@Van was free at pH 7.4, but assembled at pH 5.5 owing to surface charge switching from negative to zero, resulting in remarkably enhanced near-infrared (NIR) absorption and photothermal properties. CNDs@Van exhibited good biocompatibility, low cytotoxicity, and weak hemolytic effects under physiological conditions (pH 7.4). Regarding targeted binding to VRE bacteria, CNDs@Van self-assembled in a weakly acidic environment (pH 5.5) generated by VRE biofilms, giving enhanced photokilling effects in in vitro and in vivo assays. Therefore, potentially, CNDs@Van can be used as a novel antimicrobial agent against VRE bacterial infections and their biofilms.