Intracellular release of anticancer agents from a hollow silica nanocontainer with glutathione-responsive cyclodextrin gatekeepers

We report preparation and intracellular release characteristics of the hollow mesoporous silica (HMS) nanoparticles composed of a hollow core, a mesoporous silica shell, and surface cyclodextrin (CD) gatekeepers connected with a glutathione (GSH)-responsive disulfide linker. The hollow core provided a large empty space with the capability of high drug loading. The CD gatekeepers kept the guest molecules in the hollow core and the nanochannel without releasing guests until an external stimulus was applied. Upon triggering by GSH, the disulfide bond on the surface of HMS was cleaved and the guest drug molecules were released. We also observed the effective intracellular release of DOX by HMS-SS-DOX-CD-PEG in the A549 cells which was found to express GSH at high levels. Furthermore, HMS-SS-DOX-CD-PEG increased cell death in a dose dependent manner.