Redox-Responsive Delivery System for Prodrugs

Redox-responsive drug delivery systems (DDSs) have emerged as powerful platforms for the site-specific and stimuli-triggered activation of prodrugs, particularly within pathological microenvironments characterized by aberrant redox states. This chapter provides a comprehensive analysis of redox-cleavable linkers, such as disulfide, diselenide, tetrasulfide, and succinimide-thioether bonds, engineered into nanocarriers to facilitate the intracellular release of prodrugs in response to elevated glutathione (GSH) concentrations. Emphasis is placed on the chemical rationale underpinning linker cleavage, the structural optimization of prodrug conjugates, and the controlled activation mechanisms in reductive environments. The integration of these responsive elements into polymeric micelles, liposomes, nanogels, and mesoporous carriers is discussed with a focus on their efficacy in enhancing prodrug stability, bioavailability, and therapeutic precision. This chapter aims to delineate current advancements and critical considerations in the rational design of redox-activated prodrug systems for targeted therapy.