Butyrylcholinesterase nanodepots with enhanced prophylactic and therapeutic performance for acute organophosphorus poisoning management

Acute organophosphorus pesticide poisoning (AOPP) is a worldwide health concern that has threatened human lives for decades, which attacks acetylcholinesterase (AChE) and causes nervous system disorders. Classical treatment options are associated with shortin vivohalf-life and side effects. As a potential alternative, delivery of mammalian-derived butyrylcholinesterase (BChE) offers a cost-effective way to block organophosphorus attack on acetylcholinesterase, a key enzyme in the neurotransmitter cycle. Yet the use of exotic BChE as a prophylactic or therapeutic agent is compromised by short plasma residence, immune response and unfavorable biodistribution. To overcome these obstacles, BChE nanodepots (nBChE) composed of a BChE core/polymorpholine shell structure were preparedvia in situpolymerization, which showed enhanced stability, prolonged plasma circulation, attenuated antigenicity and reduced accumulation in non-targeted tissues.In vivoadministration of nBChE pre- or post-organophosphorus exposure in a BALB/C mouse model resulted in potent prophylactic and therapeutic efficiency. To our knowledge, this is the first systematic delivery of non-human BChE to tackle AOPP. In addition, this work also opens up a new avenue for real applications in both research and clinical settings to cope with acute intoxication-related diseases.