Nanotherapeutics for hydrogen sulfide-involved treatment: An emerging approach for cancer therapy

Hydrogen sulfide (H2S), as the third gasotransmitter, plays important roles in promoting the growth, proliferation, and metastasis of cancer cells. Recently, emerging nanotherapeutics have been developed for cancer therapy by regulating the H2S concentration at tumor sites. The action of H2S in cancer therapy can be demonstrated by a bell-shaped dose-response curve. In addition to the H2S donation from gas therapy, reducing the level of intratumoral H2S can also exert an antitumor effect by disturbing the redox balance of tumor cells. On top of that, the integration of nanotechnology further enhances the diversity of H2S-involved cancer treatments. As a result, phototherapy, chemotherapy, immunotherapy, and ultrasonic therapy can all be realized by designing nanotherapeutics based on the physicochemical properties of H2S. Furthermore, the active/passive targeting effects and onsite H2S-regulating ability of nanotherapeutics greatly improve the safety of treatment. To track the development and promote the clinical transformation of H2S-involved nanotherapeutics, this review introduced the antitumor-related properties of H2S gas and the evolution of H2S-involved cancer therapy. Then, we discussed the design concepts and mechanisms of H2S-involved nanotherapeutics in depth. Finally, the future expectations and challenges were spotlighted in the concept of translational medicine.