Triple cell-responsive nanogels for delivery of drug into cancer cells

In this report, biocompatible nanogels with multi cell-responsiveness (thermo-, pH- and reduction) were fabricated by in situ cross-linking of alginate (AG) using cystamine (Cys) as a cross-linker through an emulsion approach, in the presence of a thermosensitive polymer, poly(N-isopropylacrylamide) (PNIPAM). The AG/PNIPAM nanogels exhibited an abrupt swelling upon temperature increase from 37 to 25 °C under physiological conditions (497 ± 258 nm at 29 °C and 147 ± 48 nm at 37 °C). The nanogels were easily taken up by cancer cells at high temperature, where temperature variation could induce toxicity against cancer cells. Furthermore, the accelerated release under reducible and acidic microenvironments inside cells, together their thermosensitivity, made the nanogels selectively deliver drug intracellulary to exert a synergistical anticancer efficacy, potentiating therir high promise for drug delivery application.