Preparation of pH-Responsive Mesoporous Silica Nanoparticles and Their Application in Controlled Drug Delivery

Poly(acrylic acid) grafted mesoporous silica nanoparticles (PAA-MSNs) were prepared by a facile graft-onto strategy, i.e., the amidation between PAA homopolymer and amino group functionalized MSNs. The resultant PAA-MSNs were uniform spherical nanoparticles with a mean diameter of approximately 150 nm, and the graft amount of PAA evaluated by thermogravimetric analysis (TGA) was about 12 wt %. Due to the covalent graft of hydrophilic and pH-responsive PAA, the PAA-MSNs could be well dispersed in aqueous solution, which is favorable to be utilized as drug carriers to construct a pH-responsive controlled drug delivery system. N-2 adsorption-desorption isotherm results demonstrated that doxorubicin hydrochloride (DOX), a well-known anticancer drug, could be effectively loaded into the channels of PAA-MSNs through the electrostatic interaction. The loading content and the entrapment efficiency of DOX could reach up to 48% and 95%, respectively. The drug release rate of DOX@PAA-MSN was pH dependent and increased with the decrease of pH. The in vitro cytotoxicity test indicated that PAA-MSNs were highly biocompatible and suitable to use as drug carriers. The drug-loaded DOX@PAA-MSNs were distinctly cytotoxic to HeLa cells, due to the sustained release of drug, and showed higher clinical effects than free DOX. These results imply that the PAA-MSNs are promising platforms to construct pH-responsive controlled drug delivery systems for cancer therapy.