Zhou Hui, Gong Youcong, Liu Yanan, Huang Anlian, Zhu Xufeng, Liu Jiawei, Yuan Guanglong, Zhang Li, Wei Ji-An, Liu Jie
Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, China.
Joint International Research Laboratory of CNS Regeneration, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China.
Biomaterials. 2020 Apr;237:119822. doi: 10.1016/j.biomaterials.2020.119822. Epub 2020 Jan 24.
Alzheimer's disease (AD) seriously affects human health and life and lacks effective treatments. The lessons of many clinical trial failures suggest that targeting amyloid beta to treat AD is difficult, and finding new targets is an important direction for AD drug research. The neurofibrillary tangles formed by hyperphosphorylation of tau protein induce the production of cytotoxic reactive oxygen species (ROS) and cause neuronal apoptosis. Therefore, inhibition of hyperphosphorylation of tau protein and reduction of neuronal damage have become promising methods for the treatment of AD. We herein designed a novel nanocomposite with high stability and good biocompatibility by using flower-shaped hollow nano-ruthenium (Ru NPs) as a carrier, loading nerve growth factor (NGF) and sealing with phase change material (PCM). Due to its excellent photothermal effect, under the near-infrared (NIR) irradiation, the nanocomposite could effectively penetrate the blood-brain barrier (BBB) and respond to phase changes in the lesion area, releasing NGF, which inhibited tau hyperphosphorylation, reduced oxidative stress, and more importantly restored nerve damage and maintained neuronal morphology, thereby significantly improving learning and memory in AD mice. Thus, the experimental results indicate that multifunctional nanocomposites may be a promising drug in the treatment of AD.
阿尔茨海默病（AD）严重影响人类健康和生活，且缺乏有效的治疗方法。许多临床试验失败的教训表明，以β淀粉样蛋白为靶点治疗AD颇具难度，寻找新的靶点是AD药物研究的一个重要方向。tau蛋白过度磷酸化形成的神经原纤维缠结会诱导细胞毒性活性氧（ROS）的产生并导致神经元凋亡。因此，抑制tau蛋白的过度磷酸化以及减少神经元损伤已成为治疗AD的有前景的方法。我们在此设计了一种新型纳米复合材料，以花状空心纳米钌（Ru NPs）为载体，负载神经生长因子（NGF）并用相变材料（PCM）进行封装，该复合材料具有高稳定性和良好的生物相容性。由于其优异的光热效应，在近红外（NIR）照射下，纳米复合材料能够有效穿透血脑屏障（BBB）并对病变区域的相变做出响应，释放NGF，从而抑制tau蛋白过度磷酸化，减轻氧化应激，更重要的是修复神经损伤并维持神经元形态，进而显著改善AD小鼠的学习和记忆能力。因此，实验结果表明多功能纳米复合材料可能是治疗AD的一种有前景的药物。
