Antimicrobial, Anti-inflammatory, Angiogenesis, and Wound Healing Activities of Copper Nanoparticles Green Synthesized by <i>Lupinus arcticus</i> Extract

Abstract

Background: Wound healing and antibiotic resistance of pathogenic microbes have become global issues with serious consequences for the treatment of infectious diseases. Objectives: The present study aimed to evaluate the antibacterial, anti-inflammatory, angiogenic, and wound healing properties of copper nanoparticles (CuNPs) synthesized using Lupinus arcticus extract. Methods: The green synthesis was conducted using the precipitation method. The antibacterial activity of CuNPs against both methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) strains was evaluated. The effects of CuNPs on protein leakage, the expression levels of biofilm-related genes [e.g., intracellular adhesion A (icaA), intracellular adhesion D (icaD), and elastin-binding protein (EbpS) genes] in MRSA, as well as its impact on wound healing, angiogenesis, and anti-inflammatory effects, were assessed. Results: The CuNPs exhibited a spherical shape with dimensions ranging from 10 to 85 nm. Both CuNPs alone and in combination with gentamicin (GNT) inhibited biofilm formation in MRSA, with minimum biofilm inhibitory concentration (MBIC50) values of 6.6 µg/mL and 0.50 µg/mL for MRSA, respectively. The CuNPs significantly (P < 0.05) downregulated the expression levels of icaA, icaD, and EbpS in MRSA, particularly at half the minimum inhibitory concentration (1/2 MIC) and the minimum inhibitory concentration (MIC). Additionally, CuNPs markedly (P < 0.001) increased protein leakage in MRSA. The CuNPs demonstrated potent in vitro wound healing effects, promoting fibroblast cell proliferation and wound closure in a dose-dependent manner. Our results indicated a significant (P < 0.05) increase in the expression of HLA-G5 and VEGF-A genes in cells exposed to CuNPs. Furthermore, CuNPs reduced the expression levels of inflammatory genes in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (P < 0.05). Conclusions: The findings of this experimental test indicate that CuNPs, particularly in conjunction with GNT, exhibits promising antibacterial effects against MRSA without causing cytotoxicity to normal cells. This study also demonstrated that green-synthesized CuNPs possesses significant wound-healing properties through its antibacterial activity, inhibition of biofilm formation, induction of angiogenesis, and reduction of inflammation. However, further experiments are necessary to elucidate the precise mechanisms of action and potential toxicity of CuNPs.