Differential Detection of Amyloid Aggregates in Old Animals Using Gold Nanorods by Computerized Tomography: A Pharmacokinetic and Bioaccumulation Study

Int J Nanomedicine. 2023 Dec 29:18:8169-8185. doi: 10.2147/IJN.S435472. eCollection 2023.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Keywords: Alzheimer’s disease; Aβ; amyloid-beta; computed tomography; diagnostic; gold nanorods.

MeSH terms

  • Alzheimer Disease* / diagnostic imaging
  • Alzheimer Disease* / metabolism
  • Amyloid / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Bioaccumulation
  • Brain / metabolism
  • Disease Models, Animal
  • Gold / chemistry
  • Metal Nanoparticles* / chemistry
  • Mice
  • Mice, Transgenic
  • Nanotubes* / chemistry
  • Peptides / chemistry
  • Tissue Distribution
  • Tomography
  • Tomography, X-Ray Computed

Substances

  • Gold
  • Peptides
  • Amyloid
  • Amyloid beta-Peptides