Synthesis, Self‐Assembly and Drug Controlled Releasing Performance of Triple Responsive Ternary Copolymer Micelles

Abstract In order to avoid structural instability caused by the hydrolysis of spiropyran unit during responsive process, a new spiropyran monomer named as SPA was prepared by grafting carbamate functional groups to side chain of spiropyran frame. With SPA, 2‐(2‐(2‐methoxyethoxy) ethoxy) ethyl methacrylate (MEO 3 MA) and 2‐(diethylamino) ethyl methacrylate (DEAEMA) as the organic monomers, a triple responsive copolymer, P(SPA‐co‐MEO 3 MA‐co‐DEAEMA) abbreviated as PSOD, was obtained by one‐pot random copolymerization. The chemical structure, responsive behaviors and self‐assembly of the resulting copolymer were studied by a series of technical methods. With 5‐Fluoro‐2′‐deoxyuridin (FUDR) as the model anti‐cancer drug, the loading and controlled releasing behaviors of the copolymer micelles were systematically explored. Also, the cytotoxicity test and fluorescence imaging of PSOD copolymer were performed with human breast cancer cell line (MCF‐7) as the experimental subject. The results showed that the copolymer micelles had controllable drug releasing performance in complex combined stimuli conditions, and the releasing process could be well described by Korsmeyer‐Peppas model. The cytotoxicity of PSOD was proved to be relatively low, which laid a foundation for the subsequent in‐vivo drug releasing. Triple responsive performance of the copolymer micelles might provide a new inspiration for the future study of drug‐controlled releasing system.