Current state of the art in redox-sensitive polysaccharide-based prodrug scaffolds for improving therapeutic outcomes.

With an immense advancement in the therapeutic technologies, redox-responsive drug delivery systems have been extensively explored preclinically for the treatment of several critical diseases, including cancer. Particularly, considerable attention has been paid for the fabrication of polysaccharide-based prodrug scaffolds, where a variety of redox-responsive functional groups or pendants is employed to chemically conjugate small-molecule drugs with different carbohydrate polymers. The redox-responsive bonds of such scaffolds could be cleavable at the microenvironmental elevated glutathione (GSH) and reactive oxygen species (ROS) concentrations, triggering a rapid molecular conformational change and release of the bioactive cargos at the targeted sites and eventually minimize the systemic toxic effects. The present article provides an insight into the rational design and fabrication of recently developed redox-responsive polysaccharide-based prodrug scaffolds and their improved bio-performances relative to their therapeutic precursors, following a comprehensive overview on microenvironmental dysregulated redox homeostasis and various redox-responsive motifs. The prospects and challenges of these conjugates are also briefly discussed for future development of promising redox-responsive nanomedicines.