Glutathione‐Mediated Degradation of Surface‐Capped MnO2 for Drug Release from Mesoporous Silica Nanoparticles to Cancer Cells

Owing to its higher concentration in cancer cells than that in the corresponding normal cells, glutathione (GSH) provides an effective and flexible mechanism to design drug delivery systems. Here a novel GSH-responsive mesoporous silica nanoparticle (MSN) is reported for controlled drug release. In this system, manganese dioxide (MnO2) nanostructure, formed by the reduction of KMnO4 on the surface of carboxyl-functionalized MSN can block the pores (MSN@MnO2). By a redox reaction, the capped MnO2 nanostructure can dissociate into Mn2+ in the presence of GSH molecules. The blocked pores are then uncapped, which result in the release of the entrapped drugs. As a proof-of-concept, doxorubicin (DOX) as model drug is loaded into MSN@MnO2. DOX-loaded MSN@MnO2 shows an obvious drug release in 10 × 10−3 m GSH, while no release is observed in the absence of GSH. In vitro studies using human hepatocellular liver carcinoma cell line (HepG2) prove that the DOX-loaded MSN@MnO2 can entry into HepG2 cells and efficiently release the loaded DOX, leading to higher cytotoxicity than to that of human normal liver cells (L02). It is believed that further developments of this GSH-responsive drug delivery system will lead to a new generation of nanodevices for intracellular controlled delivery.