Intelligent polymeric hydrogen sulfide delivery systems for therapeutic applications

Hydrogen sulfide (H₂S) plays an important role in regulating various pathological processes such as protecting mammalian cell from harmful injuries, promoting tissue regeneration, and regulating the process of various diseases caused by physiological disorders. Studies have revealed that the physiological effects of H₂S are highly associated with its concentrations. At relatively low concentration, H₂S shows beneficial functions. However, long-time and high-dose donation of H₂S would inhibit regular biological process, resulting in cell dysfunction and apoptosis. To regulate the dosage of H₂S delivery for precision medicine, H₂S delivery systems with intelligent characteristics were developed and a variety of biocompatibility polymers have been utilized to establish intelligent polymeric H₂S delivery systems, with the abilities to specifically target the lesions, smartly respond to pathological microenvironments, as well as real-timely monitor H₂S delivery and lesion conditions by incorporating imaging-capable moieties. In this review, we focus on the design, preparation, and therapeutic applications of intelligent polymeric H₂S delivery systems in cardiovascular therapy, inflammatory therapy, tissue regenerative therapy, cancer therapy and bacteria-associated therapy. Strategies for precise H₂S therapies especially imaging-guided H₂S theranostics are highlighted. Since H₂S donors with stimuli-responsive characters are vital components for establishing intelligent H₂S delivery systems, the development of H₂S donors is also briefly introduced.