-S-S- Cleavable Linkers

Recently, -S-S- reduction sensitive nanoparticles have attracted a lot of interest to address the problem of fast drug release in cells. Such nanoparticles typically consist of a drug-loaded core and a hydrophilic shell, introducing disulfide bonds into the carrier backbone, side chains, or crosslinkers. Disulfide bond can exist stably outside the cell, but when the nanoparticles enter into the tumor cells, they can exchange disulfide bond with the high concentration of glutathione (GSH) in the cytoplasm, resulting in the disulfide bond breaking and the destruction of the carrier structure, so as to achieve the purpose of rapid drug release. Disulfide bond breakage can occur not only in the cytoplasm, but also in lysosomes, due to the presence of gamma-interferon-induced lysosomal mercaptan (GILT), which can reduce disulfide bonds.