Recently, Dr. Xingyue Ji and Dr. Zhiyuan Zhong from the College of Pharmaceutical Science collaboratively published a review article entitled “External stimuli-responsive gasotransmitter prodrugs: Chemistry and spatiotemporal release” in theJournal of Controlled Release.

Figure 1. External stimuli responsive gasotransmitter prodrugs for temporospatial release

Gasotransmitters such as NO, CO, and H₂S are endogenously generated gaseous molecules carrying important signaling information. Ample studies have already established that other endogenously generated gaseous molecules such as SO₂, CH_4,and H₂are also broadly involved in the modulation of physiological functions and are emerging as potential members of the gasotransmitter family. In addition to their physiological functions, such gasotransmitters also exhibit therapeutical potential against a series of human diseases, some of which have been approved for clinical usage (i.e., nitroglycerin for heart attack). However, due to the chemical instability and toxicity issues, these gasotransmitters must be delivered to the action site with precisely controlled dosage for ultimate clinical translation. Although the endogenous stimuli-responsive prodrug strategy partially addresses the issues associated with dosage control, it normally leads to off-target side effects thanks to the ubiquitous nature of the endogenous stimuli employed. Moreover, the levels of the endogenous stimuli vary from individual to individual, and thus the dosage can hardly be precisely controlled among different subjects. In contrast, external stimuli can mitigate these two limitations. In recent years, the external stimuli-responsive prodrug strategy has found widespread applications in the delivery of gasotransmitters. From the standpoint of medicinal chemistry, this review highlighted these advances and summarized the pros and cons of different strategies.

Figure 2.External stimuli responsive gasotransmitter prodrugs to treat human diseases

Reference：

Xingyue Ji* and Zhiyuan Zhong*. External stimuli-responsive gasotransmitter prodrugs: Chemistry and spatiotemporal release,J. Control. Release, 2022, 351, 81-101.https://doi.org/10.1016/j.jconrel.2022.09.026

About the corresponding authors:

Dr. Xingyue Ji is a distinguished professor at the Department of Medicinal Chemistry.His research interests encompass the development of gasotransmitter prodrugs, bioorthogonal prodrugs, and anti-infective and anticancer agents.He has co-authored over 40 peer-reviewed papers in some high-ranked journals, includingNat .Chem.,Angew.Chem.,J. Med. Chem.andJ. Control. Release,among others.

Dr. Zhiyuan Zhong is the Dean of the College of Pharmaceutical Sciences and serves as the Associate Editor forJ. Control. Release(IF 11.467). His research interests focused on controlled drug release and targeted cancer therapy and immunotherapy. Dr. Zhong has already published over 300 peer-reviewed papers with over 23000 citations and an H-index value of 79.