Controlling the premature release of hydrophobic drugs like quercetin over physiological conditions remains a challenge that motivates the development of smart and responsive drug carriers in recent years. This present work designed and engineered the surface of mesoporous silica nanoparticles (MSNs) by a functional compound having both amines (as a positively charged group) and carboxylic (negatively charged group), namely 4-((2-aminoethyl)amino)-4-oxobut-2-enoic acid (AmEA) prepared via simple mechanochemistry approach. The physical, textural, and morphological of MSN and MSN-AmEA were characterized by TGA, N2 adsorption-desorption, PSA-zeta, SEM, and TEM. The impact of surface modification toward textural and morphological features caused a significant decrease of BET surface area from 1038.53 m2 g− 1 (MSN) to 858.41 m2 g− 1 (MSN-AmEA). Nevertheless, the colloidal stability of MSN-AmEA is greatly improved showing by high zeta-potential especially at pH 4 compared to MSN. the effective loading capacity of MSN-AmEA was better than MSN, about 118% in comparison. Also, in contrast to MSN, MSN-AmEA prevent quercetin release at pH 7 while it is easier release at pH 4, thanks to the presence of the functional groups that has pose sensitive interaction hence it may fully control the quercetin release, as elaborated by the DFT study. Therefore, the controlled release of quercetin over MSN-AmEA verified its capability of acting as a smart drug delivery system.