Abstract：
Neurotoxins are known for their extreme lethality. However, due to their enormous diversity, effective and broad-spectrum countermeasures are lacking. This study presents a dual-modal cellular nanoparticle (CNP) formulation engineered for continuous neurotoxin neutralization. The formulation involves encapsulating the metabolic enzyme N-sulfotransferase (SxtN) into metal-organic framework (MOF) nanoparticle cores and coating them with a natural neuronal membrane, termed \"Neuron-MOF/SxtN-NPs\". The resulting nanoparticles combine membrane-enabled broad-spectrum neurotoxin neutralization with enzyme payload-enabled continuous neurotoxin neutralization. The studies confirm the protection of the enzyme payload by the MOF core and validate the continuous neutralization of saxitoxin (STX). In vivo studies conducted using a mouse model of STX intoxication reveal markedly improved survival rates compared with control groups. Furthermore, acute toxicity assessments show no adverse effects associated with the administration of Neuron-MOF/SxtN-NPs in healthy mice. Overall, Neuron-MOF/SxtN-NPs represent a unique biomimetic nanomedicine platform poised to effectively neutralize neurotoxins, marking an important advancement in the field of countermeasure nanomedicine.
摘要：
神经毒素以其极端的杀伤力而闻名。然而,由于其巨大的多样性，缺乏有效和广谱的对策。这项研究提出了一种设计用于连续神经毒素中和的双峰细胞纳米颗粒（CNP）制剂。该制剂涉及将代谢酶N-磺基转移酶（SxtN）封装到金属有机框架（MOF）纳米颗粒核心中，并用天然神经元膜包被它们，称为“神经元-MOF/SxtN-NP”。所得的纳米颗粒将膜激活的广谱神经毒素中和与酶有效载荷激活的连续神经毒素中和组合。研究证实了MOF核心对酶有效负载的保护，并验证了毒素毒素（STX）的连续中和。使用STX中毒小鼠模型进行的体内研究显示，与对照组相比，存活率显着提高。此外，急性毒性评估显示,在健康小鼠中没有与Neuron-MOF/SxtN-NP给药相关的不良反应.总的来说,神经元-MOF/SxtN-NP代表了一个独特的仿生纳米医学平台，可以有效地中和神经毒素，标志着对策纳米医学领域的重要进步。
