Aptamer‐Encapsulated Cellular Nanoparticles for Neurotoxin Neutralization

Abstract Aptamers are single‐stranded oligonucleotides that fold into defined architectures for specific target binding. In this study, aptamers are selected that specifically bind to small‐molecule neurotoxins and encapsulate them into cell membrane‐coated nanoparticles (referred to as ‘cellular nanoparticles’ or ‘CNPs’) for effective neutralization of neurotoxins. Specifically, six different aptamers are selected that bind to saxitoxin (STX) or tetrodotoxin (TTX) and encapsulate them into metal–organic framework cores, which are then coated with neuronal cell membrane. The resulting CNPs exhibit high colloidal stability, minimal aptamer leakage, and effective protection of aptamer payloads against enzyme degradation. This detoxification platform combines membrane‐enabled broad‐spectrum neutralization with aptamer‐based specific toxin binding, offering dual‐modal neutralization mechanisms for efficient neurotoxin neutralization. The in vitro neutralization efficacy is demonstrated using a neuron osmotic swelling assay, a Na + flux fluorescence assay, and a cytotoxicity assay. The in vivo neutralization efficacy is further validated using mouse models of STX and TTX intoxication in both therapeutic and preventative regimens. Overall, integrating aptamers with CNPs combines the strengths of both technologies, resulting in a robust solution for broad‐spectrum toxin‐neutralization applications.