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Updated: Jan 12, 2026

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基于微量胺关联受体的鼻到大脑siRNA输送,用于改善认知功能

Liangliang Cai¹, Shanshan Li², Cheng Wan¹

¹Pharmacy School of Nantong University, Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong 226001, China.

Journal of controlled release : official journal of the Controlled Release Society

|November 2, 2025

概括

这项研究引入了新的纳米颗粒用于基因治疗的鼻至脑传递,通过向Alox12B和减少神经元损伤,有效治疗辐射诱导的脑损伤.

科学领域:

神经科学是一个神经科学.
纳米技术纳米技术
基因治疗基因治疗

背景情况:

中枢神经系统 (CNS) 疾病需要有效的药物输送穿过血脑屏障 (BBB).
鼻到脑的输送提供了一个有希望的替代方案,可以绕过BBB进行向的中枢神经系统治疗.
辐射诱导的大脑损伤 (RBI) 在中枢神经系统治疗中提出了重大挑战.

研究的目的:

开发一种用于小干扰RNA (siRNA) 的新型鼻至脑输送系统,用于治疗辐射诱导脑损伤 (RBI).
为了设计精氨酸修饰的人参衍生的细胞外囊泡 (S-GEVs) 纳米粒子 (S-GEVs@siRNA) 增强的siRNA传递准Alox12B.

主要方法:

在RBI小鼠中,RNA测序确定了p53信号通路和Alox12B上调.
人参衍生的细胞外囊泡 (GEV) 的精子胺修饰增强了嗅觉受体-痕氨基关联受体 (TAAR) 的向.
鼻内注射S-GEVs@siRNA促进了嗅觉受体神经元 (ORN) 的吸收,随后进入大脑.

主要成果:

S-GEVs@siRNA纳米粒子通过嗅觉神经通路被ORN有效地内化并进入大脑.
这些纳米粒子成功降低了Alox12B表达的调节,减少了p53-介导的神经元铁亡.
在RBI模型中,治疗显著改善了突触功能,并缓解了认知功能障碍.

结论:

S-GEVs@siRNA纳米颗粒为中枢神经系统疾病提供了有效的鼻至大脑输送策略.
该系统显示神经保护作用,并缓解与RBI相关的认知缺陷.
开发的纳米颗粒有可能通过向基因疗法治疗各种中枢神经系统疾病.

关键词:

中枢神经系统疾病中枢神经系统疾病人参衍生的细胞外囊泡.鼻子到大脑的输送神经神经铁灭菌.小的干扰RNA可以干扰RNA.微氨基关联受体的痕迹

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