Dynamic covalent linked triblock copolymer micelles for glutathione-mediated intracellular drug delivery

Redox-responsive linkages dispersed in the backbones of the synthetic polymers, while young in the current spectrum of the biomedical application, are rapidly extending into their niche. In the present work, triblock copolymer PEG-PLA-PEG synthesized and characterized by 1 H -NMR and SEC can self-assemble into redox-responsive micelles in aqueous media with nanosized 33   nm and 47   nm. And the copolymers PEG 2000 -PLA 3000 -PEG 2000 and PEG 2000 -PLA 5000 -PEG 2000 present lower CMC with 0.034 and 0.022   mg/mL, and higher DLC of 4.28% and 5.14% respectively, compared with that of diblock copolymer. Moreover, drug release from the micelles can be triggered and significantly accelerated in reductive environment. The low cytotoxicity of redox-responsive micelles was confirmed by MTT assay against NIH 3   T3 cells. All of these results demonstrated that these polymeric micelles self-assembled from double-disulfide tethered block copolymers are promising carriers for the redox-responsive intracellular delivery of hydrophobic anticancer drugs.