Abstract：
More than 15 million out of 70 million patients worldwide do not respond to available antiepilepticus drugs (AEDs). With the emergence of nanomedicine, nanomaterials are increasingly being used to treat many diseases. Here, we report that tetrahedral framework nucleic acid (tFNA), an assembled nucleic acid nanoparticle, showed an excellent ability to the cross blood-brain barrier (BBB) to inhibit M1 microglial activation and A1 reactive astrogliosis in the hippocampus of mice after status epilepticus. Furthermore, tFNA inhibited the downregulation of glutamine synthetase by alleviating oxidative stress in reactive astrocytes and subsequently reduced glutamate accumulation and glutamate-mediated neuronal hyperexcitability. Meanwhile, tFNA promotes α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization in the postsynaptic membrane by regulating AMPAR endocytosis, which contributed to reduced calcium influx and ultimately reduced hyperexcitability and spontaneous epilepticus spike frequencies. These findings demonstrated tFNA as a potential AED and that nucleic acid material may be a new direction for the treatment of epilepsy.
摘要：
全球7000万患者中有1500多万对可用的抗癫痫药物(AED)没有反应。随着纳米医学的出现,纳米材料越来越多地用于治疗许多疾病。这里,我们报道了四面体框架核酸(tFNA)，组装好的核酸纳米颗粒，表现出优异的跨血脑屏障（BBB）抑制癫痫持续状态后小鼠海马中M1小胶质细胞活化和A1反应性星形胶质细胞增生的能力。此外，tFNA通过减轻反应性星形胶质细胞的氧化应激来抑制谷氨酰胺合成酶的下调，并随后减少谷氨酸的积累和谷氨酸介导的神经元过度兴奋。同时,tFNA通过调节AMPAR内吞作用促进突触后膜中的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）内化，这有助于减少钙流入，并最终降低过度兴奋和自发性癫痫持续发作频率。这些发现证明了tFNA是一种潜在的AED，核酸物质可能是治疗癫痫的新方向。
