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.