Fang Lab publication
Neuronal cellular nanosponges for effective detoxification of neurotoxins
ACS Nano2022Vol. 1619145-19154
Summary
This preclinical study creates neuronal-membrane nanosponges as host-cell decoys for neurotoxin detoxification. Conventional antibodies and small molecules are usually designed around the structure of one toxin, making broad development difficult across a highly diverse toxin landscape. The researchers instead coated polymer cores with membrane from Neuro-2a cells. The resulting particles present the same kinds of neuronal surface features that toxins attack, encouraging the toxins to bind the sponge rather than host neurons. Tetrodotoxin served as the experimental model. In vitro, detoxification was supported by cytotoxicity, calcium-flux, and cell-swelling assays, which probe different consequences of neuronal injury. In mice exposed to tetrodotoxin, the nanosponges significantly improved survival when administered therapeutically and when used prophylactically, without reported acute toxicity. The principal finding is that function-based imitation of a vulnerable cell can neutralize a toxin without first engineering an antidote to its detailed molecular structure. This suggests a route toward broader countermeasures. However, the abstract tests only TTX, so structural independence across other neurotoxins remains a proposed advantage; binding capacity, treatment window, pharmacokinetics, chronic safety, and comparison with established antidotes are also unreported.