Molecular mechanism of enhancing antitumor activity through the interaction between monosaccharides and human serum albumin.

This study investigated the molecular mechanisms of the interactions between three antitumor active monosaccharides and human serum albumin (HSA) using spectroscopic and electrochemical analyses, supplemented by molecular docking simulations. The antitumor efficacy of these monosaccharides can be significantly enhanced by covalent drug coupling, while HSA, with its long half-life and low immunogenicity, provides new opportunities for the development of advanced antitumor drug delivery systems. The results showed that these monosaccharides effectively burst the fluorescence of HSA. Thermodynamic analysis revealed that Fucose undergoes a spontaneous, exothermic process that decreases entropy, while the binding of Mannose and Galactose is entropy-driven. Notably, the addition of these three monosaccharides slightly compacts the structure of HSA, stabilizing its transport and delivery in vivo, with the binding strength categorized as Fucose > Mannose > Galactose. These variations in binding constants explain the differences in efficacy and potential side effects in antitumor therapy. Further studies have shown that the interaction between monosaccharides and HSA improves drug stability and targeting, thereby enhancing antitumor activity. An in-depth study of these interactions may provide new insights into the design and optimization of antitumor drugs and the further development of novel antitumor therapies.