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利用多功能金纳米棒进行体内微型计算机断层扫描检测并降低淀粉样蛋白负荷:一种用于阿尔茨海默病的神经诊疗平台

In vivo micro computed tomography detection and decrease in amyloid load by using multifunctionalized gold nanorods: a neurotheranostic platform for Alzheimer's disease.

作者信息

Morales-Zavala Francisco, Jara-Guajardo Pedro, Chamorro David, Riveros Ana L, Chandia-Cristi America, Salgado Nicole, Pismante Paola, Giralt Ernest, Sánchez-Navarro Macarena, Araya Eyleen, Vasquez Rodrigo, Acosta Gerardo, Albericio Fernando, Alvarez R Alejandra, Kogan Marcelo J

机构信息

Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.

出版信息

Biomater Sci. 2021 Jun 7;9(11):4178-4190. doi: 10.1039/d0bm01825b. Epub 2021 May 13.

Abstract

The development and use of nanosystems is an emerging strategy for the diagnosis and treatment of a broad number of diseases, such as Alzheimer's disease (AD). Here, we developed a neurotheranostic nanosystem based on gold nanorods (GNRs) that works as a therapeutic peptide delivery system and can be detected in vivo for microcomputed tomography (micro-CT), being a diagnostic tool. GNRs functionalized with the peptides Ang2 (a shuttle to the Central Nervous System) and D1 (that binds to the Aβ peptide, also inhibiting its aggregation) allowed detecting differences in vivo between wild type and AD mice (APPswe/PSEN1dE9) 15 minutes after a single dose by micro-CT. Moreover, after a recurrent treatment for one month with GNRs-D1/Ang2, we observed a diminution of amyloid load and inflammatory markers in the brain. Thus, this new designed nanosystem exhibits promising properties for neurotheranostics of AD.

摘要

纳米系统的开发和应用是诊断和治疗多种疾病(如阿尔茨海默病(AD))的新兴策略。在此,我们基于金纳米棒(GNRs)开发了一种神经诊疗纳米系统,该系统可作为治疗性肽递送系统,并能在体内通过微型计算机断层扫描(micro-CT)进行检测,是一种诊断工具。用肽Ang2(一种进入中枢神经系统的穿梭肽)和D1(与Aβ肽结合并抑制其聚集)功能化的GNRs,在单次给药15分钟后,通过micro-CT能够检测野生型和AD小鼠(APPswe/PSEN1dE9)之间的体内差异。此外,在用GNRs-D1/Ang2进行为期一个月的反复治疗后,我们观察到大脑中淀粉样蛋白负荷和炎症标志物减少。因此,这种新设计的纳米系统在AD的神经诊疗方面展现出了有前景的特性。

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