Design of Controlled Drug Delivery System Based on Disulfide Cleavage Trigger

The disulfide bond has drawn increasing attention for the application on controlled drug delivery systems (CDDSs) due to its high redox sensibility, which is derived from the fact that the concentration of glutathione (GSH), a disulfide-bond-breaking agent, in the tumor tissue is 1000-fold higher than that in the blood plasma and the normal tissue. Thus, a disulfide is an ideal candidate for serving as the drug release trigger of CDDSs, which would be stable in the blood circulation and be broken when it reached the tumor tissue. However, improvements are still required in designing the structure of CDDSs and the drug loading patterns for CDDSs, which are important to the performance of CDDSs. This Feature Article briefly summarizes our recent research progress on the design and construction of CDDSs based on disulfide cleavage triggers, with different drug loading strategies (covalent and noncovalent) and carriers (copolymer and mesoporous silica nanoparticle). The controlled drug release mechanism and behaviors of these CDDSs are also discussed.