We synthesized mesoporous silica nanoparticles (MSN) with different densities of surface positive charges. The positive surface charge was generated by incorporating trimethylammonium (TA) functional groups into the framework of MSN (MSN-TA) via direct co-condensation of a TA-silane and tetraethoxysilane (TEOS) in the presence of a base as a catalyst. These MSN-TA samples have well-defined hexagonal structures with an average particle diameter of 100 nm, pore size of 2.7 nm, and surface area of about 1000 m(2) g(-1). Anionic drug molecules, Orange II (a fluorescent tracing molecule), and sulfasalazine (an anti-inflammatory prodrug used for bowel disease), were effectively loaded into these MSN-TA samples and remained inside of the MSN-TA under acidic environment (pH 2-5). The amounts of loading of both Orange II and suffasalazine were increased with increasing positive charge densities resulting from the increasing number of TA groups. When these drug-loaded MSN-TA nanoparticles were placed in physiological buffer solution (pH 7.4), a partial negative surface charge on the MSN-TA was generated due to the deprotonation of silanol groups, and the strong electrostatic repulsion triggered a sustained release of the loaded molecules. MSN-TA as a nanovehicle for pH-dependent loading and controllable release of anionic drug molecules can be used as an oral delivery drug systems targeting at intestine. These drugs can be remained trapped in the nanovehicle when passing through the stomach's acidic environment and be released in intestine where the environmental pH is close to neutral.