A biomimetic nanoparticle to “lure and kill” phospholipase A2

Summary

This preclinical study develops a biomimetic inhibitor for phospholipase A2, an enzyme whose elevated activity contributes to multiple diseases but has proven difficult to block safely. Polymeric nanoparticle cores were wrapped with modified red-blood-cell membrane containing two functional additives. Melittin, together with native membrane lipids, attracted PLA2 and encouraged enzymatic attack on the coating. Oleyloxyethyl phosphorylcholine then inhibited the enzyme during that interaction. Integrating both molecules into the particle was intended to avoid the toxicity associated with administering them freely. The resulting lure-and-kill particles suppressed PLA2-induced hemolysis in vitro. In mice challenged with a lethal dose of venom-derived PLA2, treatment also reduced hemolysis and significantly improved survival, while the formulation showed no obvious toxicity in the reported tests. The principal finding is that a decoy membrane can concentrate an enzyme at an inhibitor-bearing interface, coupling recruitment and neutralization in one structure. Its significance is a platform strategy for anti-PLA2 therapy that may be safer than free attractant or inhibitor molecules. The abstract does not establish activity against the full range of PLA2 isoforms, disease efficacy beyond venom challenge, pharmacokinetics, or comprehensive toxicology.