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Abstract Per/polysulfide species that are generated from endogenously produced hydrogen sulfide have critical regulatory roles in a wide range of cellular processes. However, the lack of delivery systems that enable controlled and sustained release of these unstable species in biological systems hinders the advancement of sulfide biology research, as well as the translation of knowledge to therapeutic applications. Here, a novel approach is developed to generate per/polysulfide species in cells by combining an H2S donor and manganese porphyrin‐containing polymeric micelles (MnPMCs) that catalyze oxidization of H2S to per/polysulfide species. MnPMCs serve as a catalyst for H2S oxidation in aerobic phosphate buffer. HPLC‐MS/MS analysis reveals that H2S oxidation by MnPMCs in the presence of glutathione results in the formation of glutathione‐SnH (n= 2 and 3). Furthermore, co‐treatment of human umbilical vein endothelial cells with the H2S donor anethole dithiolethione and MnPMCs increases intracellular per/polysulfide levels and induces a proangiogenic response. Co‐delivery of MnPMCs and an H2S donor is a promising approach for controlled delivery of polysulfides for therapeutic applications.
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Reactive Oxygen Species‐Triggered Hydrogen Sulfide Release and Cancer‐Selective Antiproliferative Effect of Anethole Dithiolethione‐Containing Polymeric Micelles
Abstract Hydrogen sulfide (H2S) is a gaseous signaling molecule in the human body and has attracted attention in cancer therapy due to its regulatory roles in cancer cell proliferation and migration. Accumulating evidence suggests that continuous delivery of H2S to cancer cells for extended periods of time suppresses cancer progression. However, one major challenge in therapeutic applications of H2S is its controlled delivery. To solve this problem, polymeric micelles are developed containing H2S donating‐anethole dithiolethione (ADT) groups, with H2S release profiles optimal for suppressing cancer cell proliferation. The micelles release H2S upon oxidation by reactive oxygens species (ROS) that are present inside the cells. The H2S release profiles can be controlled by changing the polymer design. Furthermore, the micelles that show a moderate H2S release rate exert the strongest anti‐proliferative effect in human colon cancer cells in in vitro assays as well as the chick chorioallantoic membrane cancer model, while the micelles do not affect proliferation of human umbilical vein endothelial cells. This study shows the importance of fine‐tuning H2S release profiles using a micelle approach for realizing the full therapeutic potential of H2S in cancer treatment.
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- PAR ID:
- 10439335
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- Volume:
- 12
- Issue:
- 6
- ISSN:
- 2192-2640
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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