用于神经毒素有效解毒的神经元细胞纳米海绵,ACS Nano

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用于神经毒素有效解毒的神经元细胞纳米海绵
ACS Nano ( IF 15.8 ) Pub Date : 2022-11-10 , DOI: 10.1021/acsnano.2c08319
Dan Wang ₁ , Xiangzhao Ai ₁ , Yaou Duan ₁ , Nianfei Xian ₁ , Ronnie H Fang ₁ , Weiwei Gao ₁ , Liangfang Zhang ₁

Affiliation

神经毒素会攻击并破坏神经系统，从而导致严重的健康问题和安全威胁。现有的解毒方法，如抗体和小分子解毒剂，依赖于神经毒素的分子结构作为设计线索，并且需要针对每种毒素进行毒素特异性开发。然而，神经毒素的巨大多样性使得这种基于结构的抗毒素开发特别具有挑战性且效率低下。在这里，我们报告了神经元膜包被的纳米海绵（表示为“Neuron-NS”）的开发和使用，作为一种有效的神经毒素解毒方法。具体而言，Neuron-NS 充当神经元诱饵来引诱神经毒素，与毒素结合并中和毒素，从而阻止它们攻击宿主神经元细胞。无论分子结构如何，这些纳米海绵都能解毒神经毒素，因此可以克服毒素结构多样性带来的挑战。在这项研究中，我们通过将 Neuro-2a 细胞膜涂覆到聚合物核上来制造 Neuron-NS。同时，我们选择河豚毒素 (TTX) 作为模型神经毒素，并在细胞毒性测定、钙通量测定和细胞渗透肿胀测定中证明了 Neuron-NS 的解毒功效体外。此外，在 TTX 中毒的小鼠模型中，Neuron-NS 在治疗和预防方案中显着提高了小鼠的存活率，而没有显示出急性毒性。总的来说，Neuron-NS 有助于目前的解毒武器库，具有治疗神经毒素引起的各种损伤和疾病的潜力。

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Neuronal Cellular Nanosponges for Effective Detoxification of Neurotoxins

Neurotoxins attack and destruct the nervous system, which can cause serious health problems and security threats. Existing detoxification approaches, such as antibodies and small molecule antidotes, rely on neurotoxin’s molecular structure as design cues and require toxin-specific development for each type of toxins. However, the enormous diversity of neurotoxins makes such structure-based development of antitoxin particularly challenging and inefficient. Here, we report on the development and use of neuronal membrane-coated nanosponges (denoted “Neuron-NS”) as an effective approach to detoxifying neurotoxins. Specifically, Neuron-NS act as neuron decoys to lure neurotoxins, bind with and neutralize the toxins, and thus block them from attacking the host neuron cells. These nanosponges detoxify neurotoxins regardless of their molecular structures and therefore can overcome the challenge posed by toxin structural diversity. In the study, we fabricate Neuron-NS by coating the membrane of Neuro-2a cells onto polymeric cores. Meanwhile, we select tetrodotoxin (TTX) as a model neurotoxin and demonstrate the detoxification efficacy of the Neuron-NS in a cytotoxicity assay, a calcium flux assay, and a cell osmotic swelling assay in vitro. Additionally, in mouse models of TTX intoxication, the Neuron-NS significantly enhance mouse survival in therapeutic and prophylactic regimens without showing acute toxicity. Overall, the Neuron-NS contribute to the current detoxification arsenal with the potential to treat various injuries and diseases caused by neurotoxins.

更新日期：2022-11-10

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