Glyco functionalized gold nanoparticles for mechanistic understanding antimicrobial efficacy and translational applications

Abstract There is a growing demand for alternative therapeutic strategies beyond conventional antibiotics due to the acceleration in threat of antimicrobial resistance. In recent years, carbohydrate-functionalized gold nanoparticles (glyco-AuNPs) have gained considerable interest owing to their biocompatibility, tunable surface reactivity, and broad-spectrum antimicrobial property. This review provides a comprehensive overview of the synthesis, functionalization, mechanisms of action, and biomedical applications of glyco-AuNPs using monosaccharides, oligosaccharides, and polysaccharides. The review critically evaluates the antimicrobial mechanisms of glyco-AuNPs, including membrane disruption, reactive oxygen species generation, biofilm inhibition, and targeted microbial interactions, while distinguishing experimentally validated pathways from proposed mechanisms. Current development on antibacterial, antifungal, antiviral, and wound-healing applications are discussed, with representative studies demonstrating their effectiveness against multidrug-resistant pathogens. Despite promising results, several challenges hinder clinical translation, including large-scale synthesis, reproducibility, long-term toxicity, biodistribution, pharmacokinetics, and regulatory considerations. Future opportunities in glyco-engineering, targeted drug delivery, multifunctional theranostics, and scalable green manufacturing are also highlighted. Overall, this review provides critical insights into the potential of glyco-AuNPs as next-generation antimicrobial nanotherapeutics and outlines key research directions for their successful clinical implementation.