Royal Society of Chemistry, Polymer Chemistry, 10(7), p. 1913-1921, 2016
DOI: 10.1039/c6py00057f
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Stimuli-responsive nanomaterials have a promising prospect 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 bond into polymer networks, the nanogels are endowed with an excellent redox-labile property that they can degrade efficiently into short polymer chains (Mw < 2000) in the presence of reducing agent (glutathione or dithiothreitol). The anticancer drug (doxorubicin, DOX) loaded nanogels display a well-controlled release behavior, that is, low leakage of DOX in physiological condition (only 8.1% in 48 h), while rapid and sufficient release of DOX in 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 significant inhibitive effect on tumor cells (HeLa cells).