Nanogels comprising reduction-cleavable polymers for glutathione-induced intracellular curcumin delivery

In this study, we prepared nanogels of a disulfide-cleavable polymer via polyionic complexation and genipin cross-linking and evaluated their reduction-triggered intracellular curcumin (Cur) delivery. These nanogels were stable at physiological conditions due to the formation of genipin cross-linking and helical PLL/PDC complexes and would swell/dissociate at acidic and reductive conditions due to the dissociation of PLL/PDC complexes and cleaving of disulfide bonds. The cellular uptake and intracellular release of Cur-loaded nanogels were demonstrated by tracking the fluorescent Cur and in vitro drug release studies, confirming the triggered release of Cur at acidic and reductive microenvironments in cells. The MTT, TUNEL staining, and Caspase-3 activity assays showed that the Cur-loaded nanogels exhibited higher cellular proliferation inhibition toward U-87 MG cells than free Cur, whereas the blank nanogels exhibited low cytoxicity. The results highlight the potential of functional nanogels prepared by polyionic complexation and cross-linking as a smart nanocarrier for drug delivery.