Facile preparation of cancer-specific polyelectrolyte nanogels from natural and synthetic sugar polymers

Glyco-nanogels are glycopolymer-decorated nanoparticles of three-dimensional cross-linked networks, which have attracted ever-increasing interest of the biomedical-related community. However, most of the current reported glycosylated nanogels are prepared by copolymerization of glycopolymers with co-monomers and cross-linkers. Physically self-assembled glyco-nanogels remain a big challenge and are rarely explored. Herein, we report a new synthesis of glycosylated polyelectrolyte nanogels (glyco/CS nanogels), which are self-assembled from glycopolymers (PMAG-b-PMAA) synthesized through reversible addition-fragmentation chain transfer polymerization (RAFT) and quaternary ammonium chitosan (QACS) via electrostatic interactions under physiological conditions (pH 7.4, NaCl 0.15 M). The resultant glyco-nanogels have been demonstrated to be very stable in 10 mM HEPES buffer solution at least for 7 days and possess a specific binding capability to Con A. Their structure composed of an ionically cross-linked core and a glucose corona was confirmed by TEM. Compared with normal cells, glyco/CS nanogels exhibited a much higher affinity and cytotoxicity towards K562 cancer cells. In addition, the cellular uptake of these nanogels by K562 was further imaged via fluorescent microscopy in which nanogels with yellow-green signals were found to eventually co-locate within the cell nuclei of K562. The incorporation of natural and synthetic sugar polymers into polyelectrolytes has provided an insight to easily prepare glyco-nanogels with excellent colloidal stability, specific bioactivities and imaging ability, suggesting their great potential for biomedical applications.