Synthesis of a glycoconjugate as a component of a targeted liposomal system for tumor cells.

Abstract

Cancer therapy remains limited by the low selectivity and systemic toxicity of conventional chemotherapeutic agents, highlighting the need for improved drug delivery systems. In this study, a glucose-derived glycoconjugate was synthesized and incorporated into liposomal nanocarriers to develop a functionalized liposomal platform for further investigation. A β-O-glucoside monomer bearing an acryloyl functionality was synthesized through multistep carbohydrate derivatization and subsequently polymerized by free-radical polymerization using lauroyl peroxide as initiator, yielding a glycoconjugate. The polymeric material was characterized by dynamic and static light scattering (DLS and SLS) and solution-state nuclear magnetic resonance (1H NMR). DLS analysis revealed large polymeric species and/or supramolecularly associated structures in aqueous medium, with a mean hydrodynamic radius of 277.43 nm. SLS analysis yielded an apparent molecular mass of approximately 32.1 kDa, supporting the polymeric nature of the glycoconjugate, while the negative second virial coefficient indicated a tendency toward intermolecular association in aqueous solution. The absence of well-resolved glycoconjugate resonances in the 1H NMR spectrum was consistent with restricted molecular mobility and severe signal broadening associated with high-molecular-weight species. Conventional liposomes and glycoconjugate-functionalized liposomes were prepared by the lipid film hydration method using soy phosphatidylcholine and cholesterol. Incorporation of the glycoconjugate increased the mean hydrodynamic size of the liposomes from approximately 75 nm to approximately 95 nm and substantially modified their surface charge. The hydroxyl-rich glycoconjugate layer may contribute to particle hydration and provide additional steric or solvation-related stabilization. Overall, these results support the formation of glycoconjugate-functionalized liposomes with nanoscale dimensions and modified surface properties, providing a platform for further physicochemical and biological evaluation.