应用超顺磁性纳米粒子TAT-SPIO-NAP监测Aβ沉积及探讨神经保护作用

Aβ is the key factor involved in the causation and progression of AD. Aβ may serve as an effective therapeutic target of AD. In our previous study, we established the recombinant adeno-associated virus expressing TRX1-ABAD-DP-TRX2 (TAT) aptamer, which could bind with Aβ42 and exert protective effects against intracellular Aβ42 toxicity. TAT aptamer also reduced cognitive impairment in AD transgenic mice. However, the Aβ level in the brain cannot be detected by the virus vector. In this study, we design to carry TAT by SPIO, a novel magnetic nanoparticle, and detect Aβ in vivo by MRI. NAP can reduce hyperphosphorylated tau induced microtubule destabilisation and improve cognitive function. To enhance the therapeutic effect, NAP will be linked to this nanoparticle. In vitro and in vivo experiments will be conducted to demonstrate the binding of TAT-SPIOs-NAP with Aβ, to detect Aβ in the brains of transgenic AD mice by MRI and to explore the protective effects of TAT -SPIOs-NAP. This study may provide new strategy for AD treatment.

已知Aβ是AD的关键致病因素，拮抗细胞内Aβ毒性成为AD治疗的有效策略。我们前期应用病毒载体实现了适配子TRX-ABAD-DP-TRX（TAT）的表达，并在体外实验证明了适配子TAT能够与Aβ特异性结合并拮抗Aβ毒性，动物实验也证实了TAT能够改善AD小鼠的认知功能。但病毒载体不能实现在活体脑内监测Aβ水平，故本研究拟利用超顺磁性氧化铁纳米粒子（SPIO）为载体携带TAT，结合MRI技术，以期实现无创监测转基因AD小鼠脑内Aβ水平；为了提高疗效，同时融入神经保护肽NAP，旨在对抗由过度磷酸化tau蛋白所致的微管合成障碍，延缓AD病情进展。通过体外及体内实验验证复合纳米粒子与Aβ的结合，用MRI监测AD小鼠脑内Aβ沉积，探讨其神经保护作用，为AD的治疗提供新的策略。

已知Aβ是AD的关键致病因素，拮抗细胞内Aβ毒性成为AD治疗的有效策略。我们前期应用病毒载体实现了小分子抗体scFv的表达，并在体外实验证明了scFv能够与Aβ特异性结合并拮抗Aβ毒性，动物实验也证实了能够改善AD小鼠的认知功能。但病毒载体不能实现在活体脑内监测Aβ水平，故本研究利用纳米粒子为载体携带scFv，利用其荧光特性，以期未来能实现无创监测AD小鼠脑内Aβ水平。本研究成功制备了复合纳米粒子，并通过体外及体内实验验证复合纳米粒子与Aβ的结合，证实了神经保护作用，为AD的治疗提供新的策略。