A Thermoresponsive Block Copolymer Containing a Glycopolymer Segment with Specific Cell Targeting Potential

Responsive materials have gathered significant attention in many fields including medicine, flexible electronics, smart coatings, anticounterfeiting, imaging, sensing, and even oil and gas drilling. Combining specific responsivity with other functionalities in a single material requires specific designs and efforts. Herein, a novel polymer was rationally designed and synthesized as an amphiphilic block copolymer of poly(acrylamide- co -acrylonitrile) [P(AAm- co -AN)] and poly(2-(methacrylamido)glucopyranose) (PMAG), by RAFT polymerization. The thermoresponsive block exhibited upper critical solution temperature (UCST)-type thermal transition behavior with limited aqueous solubility at low temperatures. Thus, the hydrophobic segment tended to aggregate, yielding a micellar structure with a thermoresponsive hydrophobic core and a sugar-decorated shell at low temperatures. This temperature-dependent clustering is strongly influenced by several factors. The influence of the monomer composition, the polymer concentration, and the segment size was evaluated. An increase in the acrylonitrile/acrylamide feed ratio resulted in a predictable UCST increment. Meanwhile, the glycolpolymer segment with increasing size broadened the thermal transition behavior and also gradually increased the UCST mainly due to hydrogen bonding. Consequently, the thermal transition behavior was readily manipulated by the monomer composition and glycopolymer segment size. The combination of a thermosensitive hydrophobic core and a cell targeting glycopolymer shell offers significant potential for the temperature-responsive cargo delivery to specific cells. Therefore, the cell targeting performance of the thermoreponsive micelles encapsulating a fluorescence probe (Nile Red) was evaluated on murine metastatic breast cancer cell line (EMT6) and human fibroblast cell line (L929). The micelles exhibited a 2-fold increase in cellular internalization in EMT6 cells compared to L929 cells.