Redox-stimuli responsive micelles from DOX-encapsulating polycaprolactone-g-chitosan oligosaccharide

Chitosan-based amphiphilic graft copolymers are commonly obtained by modification of chitosan backbones with synthetic polymers hampering both bioactivity and biodegradability. In this work, we report the preparation of a series of chitosan oligosaccharide-grafted copolymers (PCL-g-COs) from coupling reactions between azide-pendent polycaprolactones (PCL-N3) and reducing-end alkynyl-modified chitosan oligosaccharides (COs-alkynyl). The resulting PCL-g-COs self-organized in water into nanoscale micelles (Rh < 20 nm) having a COs shell and a PCL core. Locking of the core-micelles structure employing a disulfide-containing bis-alkyne cross-linker resulted in the formation of nano-vehicles which can be degraded in response to physiological (redox) stimuli. This feature was advantageously exploited to preferentially release an anticancer drug, doxororubicin, in response to the intracellular glutathione level.