International Journal of Nanomedicine (Dec 2023)

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

  • Jara-Guajardo P,
  • Morales-Zavala F,
  • Bolaños K,
  • Giralt E,
  • Araya E,
  • Acosta GA,
  • Albericio F,
  • Alvarez AR,
  • Kogan MJ

Journal volume & issue
Vol. Volume 18
pp. 8169 – 8185

Abstract

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Pedro Jara-Guajardo,1,2 Francisco Morales-Zavala,1,2 Karen Bolaños,1– 3 Ernest Giralt,4,5 Eyleen Araya,2,6 Gerardo A Acosta,7,8 Fernando Albericio,5,7,9 Alejandra R Alvarez,10 Marcelo J Kogan1,2 1Departamento de Quimica Farmacologica y Toxicologica, Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Santiago, Chile; 2Advanced Center for Chronic Diseases (ACCDiS), Independencia, Santiago, Chile; 3Center for Studies on Exercise, Metabolism and Cancer (CEMC), Laboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Institute of Biomedical Sciences (ICBM), University of Chile, Santiago, Chile; 4Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; 5Department of Inorganic and Organic Chemistry, University of Barcelona, Barcelona, Spain; 6Departamento de Ciencias Quimicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago, Chile; 7CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine & Department of Organic Chemistry, University of Barcelona, Barcelona, Spain; 8Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, 08034, Spain; 9School of Chemistry & Physics, University of KwaZulu-Natal, Durban, South Africa; 10Cell Signaling Laboratory, Department of Cellular and Molecular Biology, Biological Sciences Faculty, Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, ChileCorrespondence: Alejandra R Alvarez; Marcelo J Kogan, Email [email protected]; [email protected]: 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: computed tomography, gold nanorods, amyloid-beta, Aβ, Alzheimer’s disease, diagnostic

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