Systematic engineering of glyco-nanomedicine platform for targeted cancer therapy

Abstract

Cancer-targeting ligands used for nanomedicines have been limited to mostly antibodies, peptides, aptamers, and small molecules thus far. Here we report a glyconanoparticle platform with combinatorial displays of sugar moieties with remarkable cancer-targeting performance. A library of 31 artificial glycopolymers composed of either homogeneous or heterogeneous display of five different sugar moieties (β-Glc, β-Gal, α-Man, β-GlcNAc, and β-GalNAc) was converted to a library of glyconanoparticles (GlyNPs) implemented with different functional cargoes. We systematically screened and validated GlyNPs with remarkable tumor-targeting abilities for CT26, DU145, A549, and PC3 tumors. Cypate-implemented GlyNP with a combinatorial display of α-Man and β-GlcNAc demonstrated superior cancer-targeting performance and potent photothermal treatment efficacy against A549 human lung tumors. In addition, docetaxel-implemented GlyNP displaying β-Glc, β-Gal, and α-Man demonstrated effective growth suppression of DU145 human prostate tumors in a targeted manner. The results collectively demonstrated the versatility and significance of combinatorial sugar ligands for developing cancer nanomedicines and strongly suggested the GlyNP platform’s potential applicability for treating diseases beyond cancer.