An optimized mesoporous silica nanosphere-based carrier system with chemically removable Au nanoparticle caps for redox-stimulated and targeted drug delivery.

To date, numerous drug delivery systems based on mesoporous silica nanoparticles (MSNs) have been explored, but little has been done on optimizing the structure and composition of MSNs to achieve effective drug delivery for cancer cells. Ideal mesoporous drug carriers should incorporate drugs in a way that prevents pre-release in biological surroundings before reaching the targeted area, which usually requires the capping of the open ends on the surface and the incorporation of targeting ligands on the exterior of nanocarriers. In this study, an MSN-based drug carrier system was synthesized with biocompatible Au nanoparticles (NPs) as the 'hard caps', and folic acid conjugated to the surface for targeting folate receptor-overexpressed cancer cells. Disulfide bonds linking Au and MSN NPs were introduced to the MSN surface as the redox-sensitive and chemically removable components. To study the effect of structures of MSNs in drug release, three types of MSNs were compared, including hollow mesoporous silica NPs, large-pore hollow mesoporous silica NPs and typical nano-sized pores on the surface (MSN). To achieve optimal coverage of thiol groups, two methods of functionalization were compared in effecting drug loading and release in vitro. Finally, the effect of residual surfactant was also discussed in anticancer studies. Therefore, the appropriate MSN nanostructure for redox-sensitive and targeted drug delivery was optimized.