Hydrogen sulfide (H2S) is an important gaseous signaling molecule (gasotransmitter) in the human body along with nitric oxide and carbon monoxide. It has been reported that continous delivery of H2S to cancer cells suppresses cancer progression. Although the potential for H2S-based therapies has attracted growing attention, one major challenge in its therapeutic applications is the lack of H2S delivery systems that enable controlled release of H2S. To solve this problem, we develop polymeric micelles containing H2S donating-anethole dithiolethione (ADT) groups, with H2S release profiles optimal for suppressing cancer cell proliferation. The H2S release profiles can be controlled by changing the polymer design. We found that the micelles that show a moderate H2S release rate exert the strongest anti-proliferative effect in human colon cancer cells in the in vitro assays as well as the chick chorioallantoic membrane cancer model while the micelles did not affect proliferation of human umbilical vein endothelial cells. This study shows the importance of fine-tuning H2S release profiles to realize the full therapeutic potential of H2S in biomedical applications.

Polymeric micelles for hydrogen sulfide delivery and their anti-cancer activity

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