Unimolecular micelles of pH-responsive star-like copolymers for co-delivery of anticancer drugs and small-molecular photothermal agents: a new drug-carrier for combinational chemo/photothermal cancer therapy

Development of stimuli-responsive drug carriers that can efficiently retain the encapsulated drug during blood circulation and selectively release the drug in disease targets under internal and/or external stimulation is important to minimize the side effects and improve the drug efficacy. Herein, we report a nanoscale polymeric carrier based on robust and pH-responsive unimolecular micelles that are able to carry multiple functional agents such as anticancer drugs and photothermal agents for improved treatment of cancer cells through combinational chemo/photothermal therapy. Specifically, we synthesized three pH-responsive amphiphilic star-like copolymers (denoted as CPDOs), which were facilely synthesized via one-step atom transfer radical polymerization (ATRP) with pH-responsive 2-(diisopropylamino) ethyl methacrylate and hydrophilic poly[(oligo ethylene glycol) methyl ether methacrylate] as co-monomers from the core of heptakis [2,3,6-tri-o-(2-bromo-2-methyl propionyl)-bcyclodextrin] as the initiator. Then the anticancer drug doxorubicin (DOX) and a narrow-bandgap molecule benzo[1,2-c; 4,5-c'] bis[1,2,5] thiadiazole-4,7-bis(9,9-dioctyl-9H-fluoren-2-yl) thiophene (denoted as BBT-2FT) as a near-infrared photothermal agent were co-encapsulated into the CPDO polymers, resulting in stable unimolecular micelles in aqueous media. The tertiary unimolecular micelles loaded with DOX and BBT-2FT showed controllable drug release kinetics and enhanced therapeutic effect against cancer cells under co-stimulation of pH change and 808 nm laser irradiation.