Departamento de Quimica Farmacologica y Toxicologica, Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
Advanced Center for Chronic Diseases (ACCDiS), Independencia, Santiago, Chile.
Int J Nanomedicine. 2023 Dec 29;18:8169-8185. doi: 10.2147/IJN.S435472. eCollection 2023.
The development of new materials and tools for radiology is key to the implementation of this diagnostic technique in clinics. In this work, we evaluated the differential accumulation of peptide-functionalized GNRs in a transgenic animal model (APPswe/PSENd1E9) of Alzheimer's disease (AD) by computed tomography (CT) and measured the pharmacokinetic parameters and bioaccumulation of the nanosystem.
The GNRs were functionalized with two peptides, Ang2 and D1, which conferred on them the properties of crossing the blood-brain barrier and binding to amyloid aggregates, respectively, thus making them a diagnostic tool with great potential for AD. The nanosystem was administered intravenously in APPswe/PSEN1dE9 model mice of 4-, 8- and 18-months of age, and the accumulation of gold nanoparticles was observed by computed tomography (CT). The gold accumulation and biodistribution were determined by atomic absorption.
Our findings indicated that 18-month-old animals treated with our nanosystem (GNR-D1/Ang2) displayed noticeable differences in CT signals compared to those treated with a control nanosystem (GNR-Ang2). However, no such distinctions were observed in younger animals. This suggests that our nanosystem holds the potential to effectively detect AD pathology.
These results support the future development of gold nanoparticle-based technology as a more effective and accessible alternative for the diagnosis of AD and represent a significant advance in the development of gold nanoparticle applications in disease diagnosis.
开发用于放射学的新材料和工具是将该诊断技术应用于临床的关键。在这项工作中,我们通过计算机断层扫描(CT)评估了肽功能化 GNR 在阿尔茨海默病(AD)转基因动物模型(APPswe/PSENd1E9)中的差异积累,并测量了纳米系统的药代动力学参数和生物积累。
GNR 用两种肽 Ang2 和 D1 进行功能化,分别赋予它们穿过血脑屏障和与淀粉样蛋白聚集结合的特性,从而使它们成为具有巨大潜力的 AD 诊断工具。纳米系统通过静脉内给药于 4 个月、8 个月和 18 个月大的 APPswe/PSEN1dE9 模型小鼠,通过计算机断层扫描(CT)观察金纳米粒子的积累。通过原子吸收法测定金的积累和生物分布。
我们的研究结果表明,用我们的纳米系统(GNR-D1/Ang2)治疗的 18 个月大的动物与用对照纳米系统(GNR-Ang2)治疗的动物相比,在 CT 信号上有明显差异。然而,在年幼的动物中没有观察到这种区别。这表明我们的纳米系统有可能有效地检测 AD 病理。
这些结果支持基于金纳米粒子的技术的未来发展,作为 AD 诊断的更有效和更易获得的替代方法,并代表了金纳米粒子在疾病诊断中的应用的重大进展。