作者：Huanhuan Liu, Cangxia Li, Dandan Tang, Xiaonan An, Yanfei Guo, Youliang Zhao*
关键字：Graft copolymer, toroidal micelle, drug delivery
论文来源：期刊
具体来源：J. Mater. Chem. B, 2015, 3, 3959 (http://pubs.rsc.org/en/content/articlelanding/2015/tb/c5tb00473j)
发表时间：2015年
Thermo-, pH and reduction triggered drug delivery vehicles based on dual-cleavable polymeric micelles were investigated. A comblike copolymer (G3) comprising one disulfide linkage and PEG, PCL and acetal-bridged PCL-b-PNIPAM grafts was controllably synthesized by successive RAFT copolymerization, ring-opening polymerization and adductive reaction. G3 was liable to self-assemble into spherical micelles at 25 °C and toroidal micelles at 37 °C, and the aggregates formed at 37 °C could be further converted into multicompartment micelles (pH 5.3), spherical micelles (DTT) and hyperbranched or necklace-like cylinders (pH 5.3 + DTT) upon external stimuli due to the stimuli-triggered topological transformation and reaggregation of copolymer aggregates. Upon external stimuli, doxorubicin (DOX) loaded G3 and G3/β-CD (co)aggregates could exhibit accelerated drug release kinetics. The apparent release rates varied in the range 0.072–0.403 h^?1 (for G3 aggregates) and 0.142–0.458 h^?1 (for G3/β-CD coaggregates), revealing that the drug release system bearing host–guest interactions could further extend the ranges of the release rate and cumulative release. Although β-CD and G3 micelles lacked notable cytotoxicity, the cytotoxicity of DOX-loaded (co)aggregates to 4T1 cells was higher than free DOX. CLSM images revealed that DOX-loaded copolymer aggregates may enter cells via endocytosis in a manner of nanocomplexes. Our study can not only extend the potential of stimuli-cleavable copolymers toward biomedical applications but also enrich the family of multi-responsive copolymer aggregates.