Herein, the synthesis and potential application as cargo delivery systems of thermo-responsive poly(N-vinylcaprolactam) (PVCL)-based, pH-responsive poly(2-(diethylamino)ethyl) methacrylate (PDEAEMA)-based, and thermo-, and pH-responsive PDEAEMA/PVCL-based core-shell nanogels are reported. All the nanogels have been synthesized using different dextranmethacrylates (Dex-MAs) as macro-cross-linkers. Doxorubicin hydrochloride (DOXO), an anticancer drug, has been effectively loaded into nanogels via hydrogen-bonding interactions between AOH groups of DOXO and AOH groups of Dex-MA chains. Drugrelease profiles at various pHs, and the cytocompatibility of the DOXO-loaded nanogels have been assessed in vitro using cervi-cal cancer HeLa and breast cancer MDA-MB-231 cell lines. In all the cases, the DOXO release is controlled by Fickian diffusion and case-II transport, being the diffusional process dominant. In addition, DOXO-loaded nanogels are efficiently internalized by HeLa and MDA-MB-231 cells and DOXO is progressively released in time. Therefore, nanogels synthesized could be suitable and potentially useful as nanocarriers for antitumor drug delivery.