Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China; Center for Materials Synthetic Biology, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China.
Biomaterials. 2022 Sep;288:121690. doi: 10.1016/j.biomaterials.2022.121690. Epub 2022 Aug 12.
Current treatments for Alzheimer's disease (AD) that focus on inhibition of Aβ aggregation failed to show effectiveness in people who already had Alzheimer's symptoms. Strategies that synergistically exert neuroprotection and alleviation of oxidative stress could be a promising approach to correct the pathological brain microenvironment. Based on the key roles of microglia in modulation of AD microenvironment, we describe here the development of Prussian blue/polyamidoamine (PAMAM) dendrimer/Angiopep-2 (PPA) nanoparticles that can regulate the mitophagy of microglia as a potential AD treatment. PPA nanoparticles exhibit superior blood-brain barrier (BBB) permeability and exert synergistic effects of ROS scavenging and restoration of mitochondrial function of microglia. PPA nanoparticles effectively reduce neurotoxic Aβ aggregate and rescue the cognitive functions in APP/PS1 model mice. Together, our data suggest that these multifunctional dendrimer nanoparticles exhibit efficient neuroprotection and microglia modulation and can be exploited as a promising approach for the treatment of AD.
目前针对阿尔茨海默病（AD）的治疗方法侧重于抑制 Aβ 聚集，但在已经出现阿尔茨海默病症状的人群中并未显示出有效性。协同发挥神经保护和减轻氧化应激作用的策略可能是纠正病理性脑微环境的一种有前途的方法。基于小胶质细胞在调节 AD 微环境中的关键作用，我们在这里描述了普鲁士蓝/聚酰胺胺（PAMAM）树枝状大分子/血管生成肽-2（Angiopep-2，PPA）纳米粒子的开发，该纳米粒子可以调节小胶质细胞的自噬作为一种潜在的 AD 治疗方法。PPA 纳米粒子表现出优异的血脑屏障（BBB）通透性，并发挥 ROS 清除和恢复小胶质细胞线粒体功能的协同作用。PPA 纳米粒子可有效减少神经毒性 Aβ 聚集物，并挽救 APP/PS1 模型小鼠的认知功能。总之，我们的数据表明，这些多功能树枝状大分子纳米粒子具有有效的神经保护和小胶质细胞调节作用，可作为治疗 AD 的一种有前途的方法。
