Methemoglobin-albumin clusters for the treatment of hydrogen sulfide intoxication.

Hydrogen sulfide (HS) has attracted significant attention as a seed in drug development. However, HS is toxic and induces lethal acute intoxication. Here, we developed methemoglobin (metHb)-albumin clusters as detoxifying agents for HS intoxication, which were designed based on the inherent binding property of metHb with HS. The metHb-albumin clusters comprising an autoxidized ferric Hb center wrapped covalently with an average of three human serum albumins showed a similar HS binding affinity to that of naked metHb. Owing to the HS binding capability, metHb-albumin clusters suppressed cell death induced by HS exposure while maintaining mitochondrial function in H9c2 cells. In addition, lethal HS intoxication model mice were rescued by a single administration of metHb-albumin clusters, resulting from the recovery of cytochrome c oxidase activity. Furthermore, the metHb-albumin clusters possessed essential characteristics, such as adequate pharmacokinetic properties and biocompatibility, for their use as detoxifying agents against HS intoxication. In conclusion, the results obtained in this study suggest that metHb-albumin clusters are promising detoxifying agents for HS intoxication and that harnessing the inherent HS binding properties of metHb is an innovative approach to develop detoxifying agents for HS intoxication.