Hydrogen sulfide responsive phototherapy agents: design strategies and biological applications

Abstract

Hydrogen sulfide (H2S) is one of the criticalgasotransmitters,which play important roles in regular physiological processes, especiallyin vital signaling pathways. However, fluctuations in endogenous H2S concentration can be linked to serious health problems,such as neurodegenerative diseases, cancer, diabetes, inflammation,cardiovascular diseases, and hypertension. Thus, it has attracteda great deal of attention in therapeutic applications, specificallyin the field of phototherapy. Photodynamic therapy (PDT) and photothermaltherapy (PTT) are two subclasses of phototherapy, which utilize eitherreactive oxygen species (ROS) or local temperature increase upon irradiationof a photosensitizer (PS) to realize the therapeutic action. Phototherapiesoffer unique advantages compared to conventional methods; thus, theyare highly promising and popular. One of the design principles followedin new generation PSs is to build activity-based PSs, which stay inactivebefore getting activated by disease-associated stimuli. These activatablePSs dramatically improve the selectivity and efficacy of the therapy.In this review, we summarize small molecule and nanomaterial-basedPDT and PTT agents that are activated selectively by H2S to initiate their cytotoxic effect. We incorporate single modePDT and PTT agents along with synergistic and/or multimodal photosensitizersthat can combine more than one therapeutic approach. Additionally,H2S-responsive theranostic agents, which offer therapyand imaging at the same time, are highlighted. Design approaches,working principles, and biological applications for each example arediscussed in detail.