Manganese Porphyrin-Containing Polymeric Micelles: A Novel Approach for Intracellular Catalytic Formation of Per/Polysulfide Species from A Hydrogen Sulfide Donor.

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 translation of knowledge to therapeutic applications. Here, we developed a novel approach to generate per/polysulfide species in cells by combining a H2S donor and manganese porphyrin-containing polymeric micelles (MnPMCs) that catalyze oxidization of H2S to per/polysulfide species. MnPMCs served as a catalyst for H2S oxidation in aerobic phosphate buffer. HPLC-MS/MS analysis revealed 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 (HUVECs) with the H2S donor anethole dithiolethione and MnPMCs increased intracellular per/polysulfide levels and induced a proangiogenic response. Co-delivery of MnPMCs and a H2S donor is a promising approach for controlled delivery of polysulfides for therapeutic applications. This article is protected by copyright. All rights reserved.