Methemoglobin-albumin clusters for cyanide detoxification.

Sodium nitrite (NaNO) is a universal antidote for patients with cyanide poisoning. However, its use has serious drawbacks in terms of efficacy and safety. Herein, we present a promising antidote: methemoglobin (metHb)-albumin clusters. The metHb-albumin cluster is made by a metHb core wrapped by covalently bound human serum albumin. Spectral analyses proved that the metHb-albumin clusters possessed cyanide-binding properties similar to those of naked metHb. In vitro cell experiments showed that metHb-albumin clusters prevented the cyanide-induced inhibition of cytochrome c oxidase activity, resulting in a strong cytoprotective effect. In mice subjected to cyanide poisoning, metHb-albumin clusters reduced mortality and alleviated metabolic acidosis, while maintaining the activity of cytochrome c oxidase in organs; their efficacy was better than that of NaNO. Furthermore, the oxygen carrying capacity was maintained in poisoned mice treated with metHb-albumin clusters and was low in those treated with NaNO. These results indicate that metHb-albumin clusters could be a more effective and safer antidote against cyanide poisoning than NaNO.