Well-defined labile diselenide-centered poly(ε-caprolactone)-based micelles for activated intracellular drug release

Abstract

Well-defined diselenide-centered biodegradable tri-block copolymers methoxyl poly(ethylene glycol)-b-poly(ε-caprolactone)-b-methoxyl poly(ethylene glycol) (mPEG–PCL–Se)₂ were precisely synthesized by the combination of ring opening polymerization using di(1-hydroxyethylene) diselenide as a new initiator and a facile coupling reaction. The amphiphilic block copolymers enabled the formation of self-assembled micelles which revealed an excellent reductive response to glutathione (GSH) due to the unique reduction-responsive cleavage of the diselenide bond. Such GSH response ensured an enhanced release of anticancer drugs (DOX) from the micelles in simulative tumor microenvironments; moreover, the drug release could be changed to some extent through fine-tuning the chemical composition of the copolymers. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements confirmed that the DOX-loaded micelles could be efficiently taken up by oral squamous carcinoma (HN30) cells and DOX was released into the nuclei of cancer cells following 4 h of incubation. The cell viability assays showed the diselenide-containing polymers were nontoxic up to a tested concentration (400 μg mL⁻¹), while the DOX-loaded micelles exhibited an evident inhibition toward HN30 cells. Therefore, the reduction-labile biodegradable (mPEG–PCL–Se)₂ may offer an alternative platform for tumor-targeting therapy.