Research ArticleDrug Development

Nanoscavenger provides long-term prophylactic protection against nerve agents in rodents

See allHide authors and affiliations

Science Translational Medicine  02 Jan 2019:
Vol. 11, Issue 473, eaau7091
DOI: 10.1126/scitranslmed.aau7091

A long-lasting poison scavenger

Nerve agents are neurotoxic compounds found in pesticides and chemical weapons. They act by blocking the transmission of nerve impulses to the muscles. After exposure, fatal consequences occur within minutes. Now, Zhang et al. report the development of a nanoparticle-based bioscavenger (nanoscavenger) that breaks down organophosphate nerve agents into innocuous compounds. Prophylactic treatment of rats and guinea pigs with this nanoscavenger revealed its low immunogenicity and good biodistribution. Treated animals were protected from repeated exposure to the nerve agent sarin over 7 days, suggesting that this nanoscavenger might be an effective prophylactic treatment for preventing nerve agent poisoning in subjects at risk.

Abstract

Nerve agents are a class of organophosphorus compounds (OPs) that blocks communication between nerves and organs. Because of their acute neurotoxicity, it is extremely difficult to rescue the victims after exposure. Numerous efforts have been devoted to search for an effective prophylactic nerve agent bioscavenger to prevent the deleterious effects of these compounds. However, low scavenging efficiency, unfavorable pharmacokinetics, and immunological problems have hampered the development of effective drugs. Here, we report the development and testing of a nanoparticle-based nerve agent bioscavenger (nanoscavenger) that showed long-term protection against OP intoxication in rodents. The nanoscavenger, which catalytically breaks down toxic OP compounds, showed a good pharmacokinetic profile and negligible immune response in a rat model of OP intoxication. In vivo administration of the nanoscavenger before or after OP exposure in animal models demonstrated protective and therapeutic efficacy. In a guinea pig model, a single prophylactic administration of the nanoscavenger effectively prevented lethality after multiple sarin exposures over a 1-week period. Our results suggest that the prophylactic administration of the nanoscavenger might be effective in preventing the toxic effects of OP exposure in humans.

View Full Text