Recent Advances in Endogenous Gas-Responsive Drug Delivery Systems.

Recent advances in Drug Delivery Systems (DDS) have focused on minimizing systemic side effects while enhancing therapeutic precision. Endogenous gas-responsive DDS represent a promising approach that utilizes biologically active gasotransmitters, including carbon monoxide (CO), nitric oxide (NO), and hydrogen sulfide (H2S), as internal triggers for targeted drug release. These gases play crucial roles in physiological processes such as tissue repair, vasodilation, and the regulation of inflammation, underscoring their significance in biological systems. However, their therapeutic application is limited due to their high reactivity, dose-dependent toxicity, and rapid degradation. To overcome these challenges, advanced engineering strategies have been developed to design intelligent delivery platforms, including hydrogels, metal-organic frameworks, and gasresponsive polymers, which can respond selectively to disease-specific microenvironmental signals such as pH, hypoxia, and reactive oxygen species (ROS). CO-Releasing Molecules (CORMs) and H2S-releasing systems have been extensively explored as drug delivery platforms with anticancer and anti-inflammatory potential. In contrast, NO-responsive nanoparticles show significant promise in wound healing and cardiovascular tissue repair. Additionally, novel polymeric materials that undergo structural or solubility changes upon interaction with endogenous gases have demonstrated effectiveness in controlled drug delivery. This review highlights emerging concepts and recent advances in endogenous gas-responsive drug delivery systems and discusses future perspectives for their biomedical applications.