Hypoxia and temperature dually responsive random copolymers: facile synthesis, self-assembly and controlled release of drug
Amphiphilic random copolymers poly(isopropylacryamide-co-acrylic acid-co-2-nitroimidazole acrylate) (P(NIPAM-co-AA-co-NIA)) with different contents of 2-nitroimidazole (NI) group were facilely synthesized through RAFT and EDC reactions. These random copolymers self-assembled into spherical micelles at room temperature through dialysis method. NI groups exhibited stimulus responsiveness under hypoxia condition. The hydrophobicity-hydrophilicity transformation could be realized through the change of NI groups into aminoimidazole (AI) groups. Moreover, NIPAM segments endowed the copolymers with thermo-responsive property. In addition, the content of NI group in the copolymers would influence the hydrophilic-hydrophobic equilibrium of the copolymers, and resultingly generated an obvious effect on the self-assembly behaviour of the copolymers and the morphologies of the self-assemblies. The micelles or vesicles can be used as the drug carriers to realize the controlled release of doxorubicin (DOX). The in vitro cell viability study of the DOX-loaded self-assemblies indicated the cytotoxicities under hypoxic condition were much higher than those under normoxic condition. Moreover, the drug release behaviors also could be adjusted by changing the temperatures. Therefore, these random copolymers are expected to be the multifunctional and smart carrier for the elimination of cancer cells.