In this study, we describe the synthesis of a new structure of pH-sensitive H40 based nanogel by click reaction through mini-emulsion polymerization. The nanogels were synthesized by cross coupling of H40-poly(epsilon-caprolactone) (H40-PCL) dendrimers as cores and poly(vinylpyridine) (PVP) as a pH sensitive crosslinker. The poly(ethylene glycol) (PEG) pendant group was introduced at the middle of PVP chains as hydrophilic segment to act as hydrophilic shell at final nanogel for better dispersity. Folic acid that is conjugated at the end of some of PEG through the free carboxyl group was used for targeting cancer cells that overexpress folate receptors. These nanogels are pH-sensitive and swelling ratio of the nanogels is closely relevant to the pH of environment. In this intracellular delivery method, the nanogel was exposed to low-pH environments of cytosol that triggered the nanogel to swell and release the drug. pH-sensitive behavior were studied by means of dynamic light scattering (DLS). Transmission electron microscopy (TEM) and DLS analysis demonstrated that the synthesized nanogels are uniform with a mean hydrodynamic diameter around 150 nm. The loading capability of the nanogels for paclitaxel (PTX), and the release pattern of the drug-loaded nanogels at different pH were investigated by UV-vis spectrometry. The folate-conjugated nanogel can be internalized by the cancer cells via folate-receptor mediated endocytosis. Cell uptake was evaluated by loading of Fluorescein as fluorescent dye into the nanogel and take fluorescent microscope photo. Cytotoxicity of the final nanogel was evaluated in vitro. The results demonstrated that the synthesized nanogel is an appropriate candidate as a nanocarrier for hydrophobic anticancer drugs. (C) 2014 Elsevier Ltd. All rights reserved.