Disulfide bond based polymeric drug carriers for cancer chemotherapy and relevant redox environments in mammals

Increasing numbers of disulfide linkage-employing polymeric drug carriers that utilize the reversible peculiarity of this unique covalent bond have been reported. The reduction-sensitive disulfide bond is usually employed as a linkage between hydrophilic and hydrophobic polymers, polymers and drugs, or as cross-linkers in polymeric drug carriers. These polymeric drug carriers are designed to exploit the significant redox potential difference between the reducing intracellular environments and relatively oxidizing extracellular spaces. In addition, these drug carriers can release a considerable amount of anticancer drug in response to the reducing environment when they reach tumor tissues, effectively improving antitumor efficacy. This review focuses on various disulfide linkage-employing polymeric drug carriers. Important redox thiol pools, including GSH/GSSG, Cys/CySS, and Trx1, as well as redox environments in mammals, will be introduced.