Metal-Organic Frameworks for Single-Dose Engineered Enzyme-Based Prophylaxis and Treatment of Organophosphate Poisoning

Organophosphate (OP) poisoning is among the most lethal forms of chemical intoxication, commonly occurring in both warfare and agricultural settings. Although enzyme-based detoxification strategies, such as organophosphorus acid anhydrolase (OPAA), have shown promise in vitro , their rapid clearance and instability have severely limited their clinical translation. Here, we report the first in vivo study demonstrating the use of metal–organic frameworks (MOFs) as delivery depots for sustained OP detoxification. OPAA was successfully encapsulated within two MOFs—zeolitic imidazolate framework-8 (ZIF-8) and NU-1003—using biomimetic mineralization and passive diffusion strategies, respectively. These composites provided prolonged subcutaneous retention, preserved enzymatic activity, and offered complete protection in mice exposed to lethal doses of OP agents. In addition to immediate post-exposure rescue, the system also functioned as a long-acting prophylactic with minimal immunogenicity and excellent biocompatibility. This dual-use approach provides a powerful new platform for enzyme therapeutics, where both sustained activity and rapid response are required.