Glyco-Gold Nanoparticles: Merging Carbohydrate Chemistry with Gold Nanotechnology for Biomedical Applications

Gold nanoparticles (AuNPs) have emerged as highly versatile tools in nanomedicine due to the tunability of their synthesis and surface functionalization. However, challenges such as limited biodistribution, rapid clearance, and short circulation time continue to hinder their clinical translation. A key factor contributing to these limitations is the formation of a protein corona (PC) upon exposure to biological fluids, which alters nanoparticle behavior and reduces targeting efficacy [1]. To overcome this, surface modification with biologically meaningful ligands—such as endogenous carbohydrates or nutrient transport substrates—can significantly improve biocompatibility and functional performance. Among these, ABO blood group antigens are particularly attractive for their role in immune self-recognition, making them effective for reducing immune clearance and prolonging nanoparticle circulation. Additionally, ligands derived from glucose and glutamine, natural substrates for intestinal co-transporters, may modulate biological processes such as barrier integrity and inflammation [2]. In our studies, we employed both classical one-pot and photo-microfluidic approaches to synthesize ultra-small AuNPs functionalized with ABO antigen derivatives and sugars/aminoacids-based ligands [2][3][4]. These glyco-AuNPs were thoroughly characterized using transmission electron microscopy (TEM), FT-IR/ATR spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. The resulting multifunctional nanostructures demonstrate strong potential for a wide array of biomedical applications, including drug delivery, imaging, diagnostics, and targeted modulation of immune and intestinal pathways, thereby paving the way toward more precise and responsive therapeutic platforms.