Methemoglobin-albumin clusters for the treatment of hydrogen sulfide intoxication

Hydrogen sulfide (H₂S) has attracted significant attention as a seed in drug development. However, H₂S is toxic and induces lethal acute intoxication. Here, we developed methemoglobin (metHb)-albumin clusters as detoxifying agents for H₂S intoxication, which were designed based on the inherent binding property of metHb with H₂S. The metHb-albumin clusters comprising an autoxidized ferric Hb center wrapped covalently with an average of three human serum albumins showed a similar H₂S binding affinity to that of naked metHb. Owing to the H₂S binding capability, metHb-albumin clusters suppressed cell death induced by H₂S exposure while maintaining mitochondrial function in H9c2 cells. In addition, lethal H₂S 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 H₂S intoxication. In conclusion, the results obtained in this study suggest that metHb-albumin clusters are promising detoxifying agents for H₂S intoxication and that harnessing the inherent H₂S binding properties of metHb is an innovative approach to develop detoxifying agents for H₂S intoxication.