Photothermal Effect-Triggered Drug Release from Hydrogen Bonding-Enhanced Polymeric Micelles

Incorporation of noncovalent interactions into hydrophobic cores of polymeric micelles provides the micelles with enhanced physical stability and drug loading efficiency, however, it also creates obstacles for drug release due to the strong interactions between carriers and drugs. Herein, a series of amphiphilic block copolymers based on poly(ethylene glycol)- b-poly(l-lysine) (mPEG- b-PLL) with similar chemical structures, while different hydrogen bonding donors (urethane, urea, and thiourea groups) are synthesized, and their capacities for codelivery of anticancer drug (e.g., doxorubicin) and photothermal agent (e.g., indocyanine green) are investigated. The resulting hybrid micelles display decreased critical micelle concentrations (CMCs) and enhanced micelle stabilities due to the hydrogen bonding between urea groups in the polymers. Moreover, the strong hydrogen bonds between the urea/thiourea groups and drugs provide the carriers with enhanced drug loading efficiencies, decreased micelle sizes, however, slower drug release profiles as well. When exposed to the near-infrared laser irradiation, destabilization of the hydrogen bonding through photothermal effect triggers fast and controlled drug releases from the micelles, which dramatically promotes the aggregation of the drugs in the nuclei, resulting in an enhanced anticancer activity. These results demonstrate that the hydrogen bonding-enhanced micelles are promising carriers for controllable chemo-photothermal synergistic therapy.