Harnessing the synergy of copper nanoparticles and vitamin C towards the resolution of wound infection

Abstract

Copper ions have been considered to hold promise for the treatment of wound infections due to their unique characteristics that exhibit not only antibacterial activities through multiple bactericidal mechanisms but also tissue reparative activities by acting as a co-factor for many angiogenic promoters and enzymes. However, higher doses are necessary to achieve sufficient bactericidal and antibiofilm effects. The objective of this study is to develop copper nanoparticles (CuNPs) as an antimicrobial agent by harnessing the characteristics of copper and vitamin C (VC) to form a sustained catalytic cycle, leading to a significant enhancement of bactericidal and antibiofilm effects when compared with the use of CuNPs alone. Specifically, our results demonstrate that CuNPs, when properly combined with a high dose of VC (>1 mM), can synergistically enhance antibacterial activity by increasing the generation of intracellular reactive oxygen species (ROS) in bacterial cells, effectively targeting a broad spectrum of bacteria. Additionally, the use of Pluronic F-127 gel has made it facile for encapsulating a defined amount of CuNP and VC to the hydrogel for topical application, which exhibits potent antibacterial and antibiofilm effects assessed by well diffusion assay and colony biofilm assay, respectively. Finally, the in vivo evaluation of antimicrobial efficacy in the murine model of skin wound infection by S. aureus and P. aeruginosa confirms that the topical application of F-127/CuNPs/VC hydrogel can significantly reduce the bacterial burden, demonstrating the therapeutic potential of F-127/CuNPs/VC hydrogel in treating wound infections.