Spatiotemporal photo-release of hydrogen sulphide from β-carboline-derived nanoparticles for therapeutic applications

Hydrogen sulfide (H₂S) is an important gasotransmitter that plays a significant role in the regulation of various physiological activities. The therapeutic effect of H₂S is highly concentration-dependent and has recently been recognized for wound healing applications. Until now, the reported H₂S delivery systems for wound healing applications have been focused on polymer-coated cargo systems for the encapsulation of H₂S donors that are based just on endogenous stimuli-responsive systems such as pH or glutathione. These delivery systems lack spatio-temporal control and can cause premature H₂S release depending on the wound microenvironment. In this regard, polymer-coated light-activated gasotransmitter donors provide a promising and efficient means of delivering high spatial and temporal control along with localized delivery. Hence, for the first time, we developed a β-carboline photocage-based H₂S donor (BCS) and formulated it into two photo-controlled H₂S delivery systems: (i) Pluronic-coated nanoparticles loaded with BCS (Plu@BCS nano); and (ii) a hydrogel platform impregnated with BCS (Plu@BCS hydrogel). We investigated the mechanism of photo-release and the photo-regulated H₂S release profile from the BCS photocage. We found that the Plu@BCS nano and Plu@BCS hydrogel systems were stable and did not release H₂S without light treatment. Interestingly, external light manipulation, such as changing the irradiation wavelength, time, and location, regulate the release of H₂S precisely. Biological studies (in vitro) suggest that the Pluronic coating on the BCS photocage makes the donor highly biocompatible and desirable for biological applications.