ROS-responsive drug delivery systems: Harnessing redox biology for targeted therapies

AbstractReactive oxygen species play an integral role in physiological signaling but contribute to pathology when dysregulated. Elevated ROS levels in diseased tissues such as tumors, inflamed sites, and ischemic regions present unique biochemical triggers for targeted drug delivery. Furthermore, strategies utilizing exogenously generated ROS (e.g., via photodynamic action) provide an alternative route for spatiotemporal control. This review summarizes recent advances in ROS-responsive systems, beginning with the chemistry of ROS-cleavable linkers and the design of nanocarrier platforms capable of spatiotemporally controlled release. The integration of these carriers with theranostic functions is highlighted as a strategy to enhance selectivity and reduce systemic toxicity. Applications across oncology, inflammatory disorders, ischemia-reperfusion injury, and regenerative medicine illustrate the breadth of therapeutic potential. Key design considerations including sensitivity thresholds, payload compatibility, and surface functionalization are discussed alongside translational challenges such as stability, reproducibility, and scalability. Emerging opportunities, notably patient-specific redox profiling and biosensor-guided adaptive delivery are identified as promising routes to clinical translation. By bridging redox biology with materials science and nanomedicine, ROS-triggered drug delivery platforms demonstrate the capacity to exploit endogenous oxidative cues for improved therapeutic precision and safety, positioning them as a transformative approach in the development of next-generation controlled release systems.