Jara-Guajardo Pedro, Cabrera Pablo, Celis Freddy, Soler Mónica, Berlanga Isadora, Parra-Muñoz Nicole, Acosta Gerardo, Albericio Fernando, Guzman Fanny, Campos Marcelo, Alvarez Alejandra, Morales-Zavala Francisco, Kogan Marcelo J
Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380494, Chile.
Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Independencia, Santiago 8380494, Chile.
Nanomaterials (Basel). 2020 Apr 6;10(4):690. doi: 10.3390/nano10040690.
The early detection of the amyloid beta peptide aggregates involved in Alzheimer's disease is crucial to test new potential treatments. In this research, we improved the detection of amyloid beta peptide aggregates in vitro and ex vivo by fluorescence combining the use of CRANAD-2 and gold nanorods (GNRs) by the surface enhancement fluorescence effect. We synthetized GNRs and modified their surface with HS-PEG-OMe and HS-PEG-COOH and functionalized them with the D1 peptide, which has the capability to selectively bind to amyloid beta peptide. For an in vitro detection of amyloid beta peptide, we co-incubated amyloid beta peptide aggregates with the probe CRANAD-2 and GNR-PEG-D1 observing an increase in the intensity of the fluorescence signal attributed to surface enhancement fluorescence. Furthermore, the surface enhancement fluorescence effect was observed in brain slices of transgenic mice with Alzheimer´s disease co-incubated with CRANAD-2 and GNR-PEG-D1. An increase in the fluorescence signal was observed allowing the detection of aggregates that cannot be detected with the single use of CRANAD-2. Gold nanoparticles allowed an improvement in the detection of the amyloid aggregated by fluorescence in vitro and ex vivo.
早期检测与阿尔茨海默病相关的β淀粉样肽聚集体对于测试新的潜在治疗方法至关重要。在本研究中,我们通过利用CRANAD - 2和金纳米棒(GNRs)的表面增强荧光效应,结合荧光技术改进了体外和离体状态下β淀粉样肽聚集体的检测。我们合成了GNRs,并用HS - PEG - OMe和HS - PEG - COOH对其表面进行修饰,并用具有选择性结合β淀粉样肽能力的D1肽对其进行功能化。对于β淀粉样肽的体外检测,我们将β淀粉样肽聚集体与探针CRANAD - 2和GNR - PEG - D1共同孵育,观察到归因于表面增强荧光的荧光信号强度增加。此外,在与CRANAD - 2和GNR - PEG - D1共同孵育的阿尔茨海默病转基因小鼠脑切片中观察到了表面增强荧光效应。观察到荧光信号增加,使得能够检测出单独使用CRANAD - 2无法检测到的聚集体。金纳米颗粒能够改进体外和离体状态下通过荧光检测淀粉样聚集体的方法。