We report the synthesis, characterization and application of a novel biocompatible nanogel (n-Gly/pHEMA) synthesized from glycogen and 2-hydroxyethyl methacrylate using ethylene glycol dimethacrylate crosslinker. Here mesoporous silica has been used as template. The structure of the nanogel has been investigated with the help of FTIR, H-1 NMR and C-13 NMR spectroscopy. The FESEM, HR-TEM and DLS analyses exhibit that the size of the nanogel is in the range of 10-50 nm. Thermal degradation kinetics suggests the higher stability of the n-Gly/pHEMA nanogel after crosslinking. The gel strength has been assessed by measurement of rheological parameters. The native nanogel shows a good compatibility with MG-63 cell lines. The n-Gly/pHEMA nanogel can effectively load 5-fluorouracil (5-FU) with encapsulation efficiency of similar to 60% after 48 h. The intercellular release experiment demonstrates that 5-FU loaded nanogel can efficiently kill the MG-63 cancer cells. In vitro release profile demonstrates controlled release behaviour with higher 5-FU release rate at pH 5.5 compared to pH 7.4. (C) 2018 Elsevier Ltd. All rights reserved.