Fang Lab publication

Dual-modal cellular nanoparticles for continuous neurotoxin detoxification

Kai, M.; Shen, W.; Yu, Y.; Wang, D.; Zhang, J.; Wang, S.; Fang, R.H.; Gao, W.; Zhang, L.

Nano Letters2024Vol. 247515-7523

Summary

This study engineers a two-part cellular nanoparticle for sustained detoxification of saxitoxin, addressing the difficulty of countering highly potent and diverse neurotoxins. The particle contains the metabolic enzyme N-sulfotransferase, or SxtN, enclosed in a metal–organic framework core. A natural neuronal membrane forms the outer layer. The membrane is intended to intercept neurotoxins through native cellular interactions, while the protected enzyme continuously converts its target rather than relying on a finite number of binding sites. Experiments confirmed that the framework sheltered the enzyme cargo and that the complete formulation repeatedly neutralized saxitoxin. In a mouse model of STX intoxication, treated animals had markedly better survival than control groups. Acute-toxicity testing in healthy mice revealed no reported adverse effects. The main finding is that membrane decoy activity and catalytic detoxification can be integrated into one biomimetic construct, coupling broader initial capture with renewable enzymatic processing. This is significant as a design principle for countermeasure nanomedicine. However, the abstract demonstrates continuous conversion only for STX and does not establish enzyme kinetics in vivo, treatment windows, long-term safety, elimination of products, or actual efficacy against a broader toxin panel.