Li Meng, Guan Yijia, Zhao Andong, Ren Jinsong, Qu Xiaogang
Laboratory of Chemical Biology, State Key Laboratory of Rare Earth Resources Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
University of Chinese Academy of Sciences, Beijing 100039, China.
Theranostics. 2017 Jul 22;7(12):2996-3006. doi: 10.7150/thno.18459. eCollection 2017.
Development of sensitive detectors of Aβ aggregates and effective inhibitors of Aβ aggregation are of diagnostic importance and therapeutic implications for Alzheimer's disease (AD) treatment. Herein, a novel strategy has been presented by self-assembly of peptide conjugated Au nanorods (AuP) as multifunctional Aβ fibrillization detectors and inhibitors. Our design combines the unique high NIR absorption property of AuNRs with two known Aβ inhibitors, Aβ15-20 and polyoxometalates (POMs). The synthesized AuP can effectively inhibit Aβ aggregation and dissociate amyloid deposits with NIR irradiation both in buffer and in mice cerebrospinal fluid (CSF), and protect cells from Aβ-related toxicity upon NIR irradiation. In addition, with the shape and size-dependent optical properties, the nanorods can also act as effective diagnostic probes to sensitively detect the Aβ aggregates. This is the first report to integrate 3 segments, an Aβ-targeting element, a reporter and inhibitors, in one drug delivery system for AD treatment.
开发敏感的Aβ聚集体探测器和有效的Aβ聚集抑制剂对于阿尔茨海默病(AD)治疗具有诊断重要性和治疗意义。在此,通过肽共轭金纳米棒(AuP)的自组装提出了一种新策略,作为多功能Aβ纤维化探测器和抑制剂。我们的设计将金纳米棒独特的近红外吸收特性与两种已知的Aβ抑制剂Aβ15 - 20和多金属氧酸盐(POMs)相结合。合成的AuP在缓冲液和小鼠脑脊液(CSF)中均可通过近红外辐射有效抑制Aβ聚集并解离淀粉样沉积物,并在近红外辐射下保护细胞免受Aβ相关毒性。此外,凭借形状和尺寸依赖的光学特性,纳米棒还可作为有效的诊断探针,灵敏地检测Aβ聚集体。这是首次在一个用于AD治疗的药物递送系统中整合三个部分,即Aβ靶向元件、报告分子和抑制剂的报告。