In the global context of increasing colonic diseases, colon specific oral drug delivery systems have shown promise as an effective therapeutic modality. Herein, we developed a mesoporous silica nanoparticle (MSN) based enzyme responsive materials for colon specific drug delivery. We have utilized guar gum, a natural carbohydrate polymer as a capping layer to contain a model drug, such as 5-flurouracil (5FU) within the mesoporous channels of MSN. Analytical characterization including electron microscopy, PXRD, nitrogen sorption, thermogravimetric analysis and FTIR, confirmed that the synthesized MSN with size less than 100 nm is of MCM-41type. The studies further showed that the MSN maintained their discrete nanoparticle identity after guar gum capping through non-covalent interaction. The release of 5FU from guar gum capped MSN (GG-MSN) was specifically triggered via enzymatic biodegradation of guar gum by colonic enzymes in the simulated colonic microenvironment. Subsequently, the released drug manifested anticancer activity in colon cancer cell lines in vitro confirmed by flow cytometry and biochemical assay. The drug loaded GG-MSN system also demonstrated near perfect ‘zero release’ property in absence of enzymes in different simulated conditions of the gastrointestinal tract. Our study provides an important intermediate step to apply such GG-MSN based engineered nanomaterials for further detailed in vivo investigation. © 2016 Elsevier B.V.