Nanoarchitectonics of cellulose nanocrystal conjugated with a tetrasaccharide-glycoprobe for targeting oligodendrocyte precursor cells.

Demyelination is a serious complication of neurological disorders, which can be reversed by oligodendrocyte precursor cell (OPC) as the available source of myelination. Chondroitin sulfate (CS) plays key roles in neurological disorders, which still attracted less attention on how CS modulates the fate of OPCs. Nanoparticle coupled with glycoprobe is a potential strategy for investigating the carbohydrate-protein interaction. However, there is lack of CS-based glycoprobe with enough chain length that interact with protein effectively. Herein, we designed a responsive delivery system, in which CS was the target molecule, and cellulose nanocrystal (CNC) was the penetrative nanocarrier. A coumarin derivative (B) was conjugated at the reducing end of an unanimal-sourced chondroitin tetrasaccharide (4mer). This glycoprobe (4B) was grafted to the surface of a rod-like nanocarrier, which had a crystalline core and a poly(ethylene glycol) shell. This glycosylated nanoparticle (N4B-P) displayed a uniform size, improved water-solubility, and responsive release of glycoprobe. N4B-P displayed strong green fluorescence and good cell-compatibility, which imaged well the neural cells including astrocytes and OPCs. Interestingly, both of glycoprobe and N4B-P were internalized selectively by OPCs when they were incubated in astrocytes/OPCs mixtures. This rod-like nanoparticle would be a potential probe for studying carbohydrate-protein interaction in OPCs.