Synergistic antimicrobial effects of polyphenolic Chinese medicine active compounds-loaded photothermal nanoparticles against multidrug-resistant Staphylococcus aureus infections.

BACKGROUND: Given the global decline in fertility rates, ensuring the healthy development of infants has become an urgent priority. Staphylococcus aureus (S. aureus) is the leading cause of lactation mastitis, a condition that often results in premature breastfeeding cessation due to the absence of effective and safe preventive measures, posing risks to infant growth and development. While antibiotics remain the primary treatment option, their overuse contributes to the emergence of antimicrobial resistance.

PURPOSE: This study aimed to develop a green, safe, and effective strategy for eradicating S. aureus and to evaluate its therapeutic efficacy in an S. aureus-induced mammary infection model.

STUDY DESIGN: This study involved an in vitro evaluation of the anti-S. aureus activity of synthetic nanoparticles, followed by an in vivo assessment of their safety, biocompatibility, and therapeutic efficacy in an S. aureus-induced mastitis model.

METHODS: Mesoporous polydopamine (mPDA) nanocarriers with responsive drug-release properties and photothermal effects were synthesized and functionalized with polyethylene glycol (PEG) to enhance dispersion stability. These PEGylated mPDA nanocarriers were subsequently loaded with the polyphenolic antimicrobial agents chlorogenic acid (CGA) or curcumin (CUR) derived from traditional Chinese medicine. The optimal molar ratios of mPDA/PEG/CGA and mPDA/PEG/CUR for achieving synergistic antibacterial effects under near-infrared (NIR) irradiation were systematically determined using a 96-well plate dilution assay. The antibacterial efficacy was further characterized through plate coating assays, while biofilm disruption was evaluated by morphological analysis and crystal violet staining across different biofilm developmental stages. Nanoparticle safety was assessed via hemolysis and mammalian cell viability assays. In vitro and in vivo models of S. aureus-induced mastitis were established to investigate therapeutic efficacy. Bacterial clearance and anti-inflammatory effects were examined through hematoxylin-eosin (HE) histopathological analysis and quantitative assessment of inflammatory cytokine gene expression.

RESULTS: The optimal antibacterial efficacy was achieved at a 5% molar ratio of CUR to CGA. Notably, the synergistic combination of CUR/CGA-loaded nanoparticles, when combined with NIR irradiation, demonstrated potent antibacterial and anti-biofilm activities against both S. aureus and methicillin-resistant S. aureus (MRSA). Furthermore, these biocompatible and safe nanoparticles, enhanced by NIR irradiation synergism, exhibited significant antimicrobial therapeutic effects, effectively ameliorating S. aureus-induced mastitis in a murine model.

CONCLUSION: This study establishes a novel multi-target, multi-modal synergistic therapeutic approach that effectively combats S. aureus infections in mammary tissue, offering a promising strategy for treating both breast and broader skin/soft tissue infections.