Pyridyl disulfide-based thiol–disulfide exchange reaction: shaping the design of redox-responsive polymeric materials

Abstract

Recent years have witnessed an increase in the utilization of stimuli-responsive polymers in various areas of materials and biological sciences. In particular, disulfide linkage containing redox-responsive polymers have attracted interest in various biomedical applications ranging from fabrication of drug delivery vehicles to diagnostic interfaces. Cleavage of the disulfide linkage in the presence of an endogenous reducing agent, namely, glutathione, also found in increased amounts in diseased tissues has led to the incorporation of this particular linkage into several therapeutic platforms. Among the various methods available for introducing the redox-sensitive disulfide unit, the pyridyl disulfide (PDS) moiety has been one of the most widely employed building blocks. The rapid thiol–disulfide exchange reaction of the PDS group with thiol functional groups has been exploited from the reversible conjugation of therapeutic agents to the fabrication of redox-responsive crosslinked materials such as hydrogels and nanogels. This review provides an overview of various synthetic approaches utilized to incorporate this particular thiol-reactive motif into different types of polymeric materials and briefly highlights its utilization to obtain functional materials.