Vancomycin modified copper sulfide nanoparticles for photokilling of vancomycin-resistant enterococci bacteria

Abstract

Due to the overuse of antibiotics, vancomycin resistant enterococci (VRE) has caused serious infections and become more and more difficult to deal with. Herein, we reported a facile one-pot strategy to synthesize copper sulfide nanoparticles using vancomycin (Van) as reductant and capping agent (CuS@Van). The as-prepared CuS@Van nanocomposites presented excellent uniformity in particle size and strong near infrared (NIR) absorbance. Fourier Transform infrared spectroscopy (FTIR) and Energy dispersive spectrometry (EDS) analysis confirmed the successful modification of Van molecules on the surface of CuS@Van nanoparticles. Bacterial TEM images verified the specific binding affinity between CuS@Van and VRE pathogen. CuS@Van also exhibited effective photokilling capability based on a combination of photothermal therapy (PTT) and photodynamic therapy (PDT). Fluorescent bacterial viability staining and bacterial growth curves monitoring were performed to explore the photokilling ablation of CuS@Van against VRE pathogens. The in vitro results indicated that CuS@Van nanocomposites had no antibacterial activity in the dark but displayed satisfying bactericidal effect against VRE pathogens upon the NIR irradiation. Mouse infection assays were also implemented to evaluate in vivo antibacterial photokilling effectiveness. CuS@Van with NIR irradiation showed the highest antibacterial capability and fastest infection regression compared with the control groups. Considering the low cost, easy preparation, good biocompatibility and excellent photokilling capability, CuS@Van nanocomposites will shed bright light on the photokilling ablation of vancomycin-resistant pathogenic bacteria.

Keywords: Copper sulfide nanoparticles; Photodynamic therapy; Photothermal therapy; Vancomycin; Vancomycin-resistant enterococci.