The synthesis, characterization, and potential application as gene delivery systems of biodegradable dual-responsive core-shell nanogels based on poly(2-diethylaminoethyl) methacrylate (PDEAEMA) and poly(N-vinylcaprolactam) (PVCL) are reported. These core-shell nanogels, having a PDEAEMA-based core and a PVCL-based shell, were synthesized by batch seeded emulsion polymerization. An indepth study of their swelling behavior was carried out, which presented a dual-dependent thermo- and pH sensitivity. Core-shell nanogels synthesized formed complexes spontaneously through electrostatic interactions when mixing with small interfering RNA (siRNA) molecules. Moreover, the core-shell nanogel/siRNA complexes showed higher polyanion exchange resistance compared to that of the PDEAEMA-based nanogel/siRNA complexes, indicating that the PVCL-based shell enhanced the stability of the complexes. In vitro siRNA release profiles showed that siRNA release was controlled by the pH of the medium as well as by the crosslinking density of the PVCL-based shell. These results indicate that dual-responsive core-shell nanogels synthesized could be potentially useful as gene delivery systems. (c) 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3203-3217