Stimuli-responsive nanostructured hydrogen sulfide donors for enhanced cancer treatments

Cancer has become one of the leading causes to human death, which promotes scientists to develop various treatment modalities. Among them, hydrogen sulfide (H₂S)-based gas therapy (GT) emerges as a facile but promising approach due to its unique merits including fast active tissue and cell penetration, robust bioactivity, negligible drug resistance. However, as a potent bioactive gas molecule, uncontrolled diffusion would significantly compromise the therapeutic efficacy and cause side effect. To address this issue, stimuli-responsive nanostructured H₂S donors, a subtype of donors capable of forming nanostructures, have been explored. Compared with unassembled ones, they could not only prolong the release time and fine tune the release rate at the aid of nanostructures, but also achieve targeting delivery of H₂S in a passive or active manner. Given that huge advancement has been made in the past few years, in this review, we survey and categorize the latest progress of these nanostructured H₂S donors for cancer treatment in terms of different constituted materials from organic to hybrid. Both H₂S-based single GT and combined therapies are examined in this review thoroughly. At the end, future outlooks and upcoming challenges of these emerging donors are discussed. We believe that it would inspire scientists to design new donors and extend their applications for human care.