Sodium Alginate Launches MOF Defective Structures to Rapidly Construct Highly AChE-Like Nanozyme for Neuroprotection

Organophosphorus (OP) nerve agents cause neurotoxicity through irreversible inhibition of acetylcholinesterase (AChE), while conventional therapeutic strategies are inadequate to fully restore cholinergic function. Artificial enzymes with AChE-like activity are urgently needed to provide sustainable catalytic capacity to address this limitation. Guided by the acid-base synergistic catalytic mechanism of the ester hydrolysis reaction, the 29-ZIF-8/SA composite with excellent AChE-like activity is successfully constructed by a defect engineering strategy with sodium alginate (SA) as a modulator. The mechanistic studies demonstrate that the basic site -OH groups introduced by SA, combined with the Lewis acid sites Zn²⁺ of ZIF-8, acted synergistically to form a bifunctional catalytic active site that enhances hydrolytic activity. Meanwhile, SA mediates the rapid formation of mesoporous architectures, improving substrate accessibility and mass transfer efficiency. In addition, 29-ZIF-8/SA demonstrates excellent environmental stability under harsh conditions and resists the inhibitory effect of methyl parathion (MP) on AChE activity. In vitro and in vivo experiments show that the 29-ZIF-8/SA composite exhibits cytoprotective properties to effectively attenuate MP-induced neurotoxicity. This work not only presents a designable method for the construction of highly active hydrolases, which are rarely reported, but also offers a new approach for nanozymes-based treatment of acute OP poisoning.