Spatiotemporal photo-release of hydrogen sulphide from -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 beta-carboline photocagebased H2S donor (BCS) and formulated it into two photo-controlled H2S delivery systems: (i) Pluroniccoated 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.