脑内纳米粒子运输由阿尔茨海默病理和年龄促进
Gregory C Tracy1, Kai-Yu Huang2, Yu-Tong Hong2
1Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Nano letters
|November 22, 2023
概括
衰老显著影响纳米粒子大脑输送对于阿尔茨海默病 (AD) 药物运输. 纳米颗粒通过穿越老年血脑屏障 (BBB) 准脑细胞,无论AD病理.
科学领域:
- 神经科学是一个神经科学.
- 生物材料科学 生物材料科学
- 药物运输 药物运输 药物运输
背景情况:
- 由于血脑屏障 (BBB) 和神经炎症,阿尔茨海默病 (AD) 对药物输送构成挑战.
- 纳米粒子设计必须考虑BBB完整性和AD中的特定大脑环境.
研究的目的:
- 为了研究衰老对纳米粒子大脑局部化和保留的影响.
- 设计能够与AD相关的反应性星体细胞和激活的微质细胞结合的纳米粒子.
主要方法:
- 开发了200纳米纳米颗粒,使用聚-乳酸-co-甘油酸 (PLGA) 和CD44结合的氨酸 (HA).
- 评估了纳米粒子与CD44表达细胞的结合.
- 在年龄 (13-16个月) 和年轻成年APP/PS1 AD模型小鼠和对照中通过静脉注射评估纳米粒子大脑定位.
主要成果:
- PLGA-b-HA纳米颗粒对反应性星球细胞和激活的微质细胞的结合增强.
- 纳米颗粒局部化到老年小鼠的海马体 (AD模型和对照) 由于增加了跨血管运输.
- 在年轻成年小鼠中没有观察到纳米粒子大脑局部.
结论:
- 血液-大脑屏障的衰老诱导的破坏促进纳米粒子进入大脑.
- 纳米粒子大脑局部化主要是由与年龄相关的BBB变化驱动的,而不是AD病理本身.
- 这些发现对于设计有效的基于纳米粒子的治疗方法来治疗与年龄相关的神经系统疾病至关重要.
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