A redox-labile poly(oligo(ethylene glycol)methacrylate)-based nanogel with tunable thermosensitivity for drug delivery

Abstract

Stimuli-responsive nanomaterials have promising prospects of application in controlled intracellular drug delivery. In this paper, we fabricated thermo- and redox-responsive biodegradable nanogels by precipitation copolymerization of 2-(2-methoxyethoxy)ethyl methacrylate, oligo(ethylene glycol)methacrylate, and a disulfide-containing crosslinker, N,N′-bis(acryloyl)cystamine. The poly(oligo(ethylene glycol)methacrylate) (POEGMA)-based nanogels exhibit a sharp volume collapse at their volume phase transition temperatures (VPTT), which are tunable in a wide temperature range. By incorporating disulfide bonds into polymer networks, the nanogels are endowed with an excellent redox-labile property that they can degrade efficiently into short polymer chains (M_w < 2000) in the presence of a reducing agent (glutathione or dithiothreitol). The anticancer drug (doxorubicin, DOX) loaded nanogels display a well-controlled release behavior, that is, low leakage of DOX under physiological conditions (only 8.1% in 48 h) and rapid and sufficient release of DOX in a reducing environment (92.2% in 48 h). Cell viability assays reveal that the blank nanogels have negligible cytotoxicity against normal cells (HEK-293T cells), while DOX-loaded nanogels present a significant inhibitive effect on tumor cells (HeLa cells).