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

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2024 Jan 3

PMID 38169997

Authors

Pedro Jara-Guajardo

Francisco Morales-Zavala

Karen Bolanos

Ernest Giralt

Eyleen Araya

Gerardo A Acosta

Fernando Albericio

Alejandra R Alvarez

Marcelo J Kogan

Affiliations

Soon will be listed here.

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.

References

Montagne A, Barnes S, Sweeney M, Halliday M, Sagare A, Zhao Z . Blood-brain barrier breakdown in the aging human hippocampus. Neuron. 2015; 85(2):296-302. PMC: 4350773. DOI: 10.1016/j.neuron.2014.12.032. View

Naz F, Koul V, Srivastava A, Gupta Y, Dinda A . Biokinetics of ultrafine gold nanoparticles (AuNPs) relating to redistribution and urinary excretion: a long-term in vivo study. J Drug Target. 2016; 24(8):720-9. DOI: 10.3109/1061186X.2016.1144758. View

Tapia-Arellano A, Gallardo-Toledo E, Ortiz C, Henriquez J, Feijoo C, Araya E . Functionalization with PEG/Angiopep-2 peptide to improve the delivery of gold nanoprisms to central nervous system: in vitro and in vivo studies. Mater Sci Eng C Mater Biol Appl. 2021; 121:111785. DOI: 10.1016/j.msec.2020.111785. View

Jara-Guajardo P, Cabrera P, Celis F, Soler M, Berlanga I, Parra-Munoz N . Gold Nanoparticles Mediate Improved Detection of β-amyloid Aggregates by Fluorescence. Nanomaterials (Basel). 2020; 10(4). PMC: 7221977. DOI: 10.3390/nano10040690. View

Pietrzak K, Czarnecka K, Mikiciuk-Olasik E, Szymanski P . New Perspectives of Alzheimer Disease Diagnosis - the Most Popular and Future Methods. Med Chem. 2017; 14(1):34-43. DOI: 10.2174/1573406413666171002120847. View

Betzer O, Shwartz A, Motiei M, Kazimirsky G, Gispan I, Damti E . Nanoparticle-based CT imaging technique for longitudinal and quantitative stem cell tracking within the brain: application in neuropsychiatric disorders. ACS Nano. 2014; 8(9):9274-85. DOI: 10.1021/nn503131h. View

Kmoch S, Stranecky V, Emes R, Mitchison H . Bioinformatic perspectives in the neuronal ceroid lipofuscinoses. Biochim Biophys Acta. 2013; 1832(11):1831-41. DOI: 10.1016/j.bbadis.2012.12.010. View

Bhavane R, Badea C, Ghaghada K, Clark D, Vela D, Moturu A . Dual-energy computed tomography imaging of atherosclerotic plaques in a mouse model using a liposomal-iodine nanoparticle contrast agent. Circ Cardiovasc Imaging. 2013; 6(2):285-94. PMC: 3760185. DOI: 10.1161/CIRCIMAGING.112.000119. View

Funke S, Bartnik D, Gluck J, Piorkowska K, Wiesehan K, Weber U . Development of a small D-enantiomeric Alzheimer's amyloid-β binding peptide ligand for future in vivo imaging applications. PLoS One. 2012; 7(7):e41457. PMC: 3404088. DOI: 10.1371/journal.pone.0041457. View

10.

Murata S, Udono H, Tanahashi N, Hamada N, Watanabe K, Adachi K . Immunoproteasome assembly and antigen presentation in mice lacking both PA28alpha and PA28beta. EMBO J. 2001; 20(21):5898-907. PMC: 125708. DOI: 10.1093/emboj/20.21.5898. View

11.

Demeule M, Currie J, Bertrand Y, Che C, Nguyen T, Regina A . Involvement of the low-density lipoprotein receptor-related protein in the transcytosis of the brain delivery vector angiopep-2. J Neurochem. 2008; 106(4):1534-44. DOI: 10.1111/j.1471-4159.2008.05492.x. View

12.

Cormode D, Roessl E, Thran A, Skajaa T, Gordon R, Schlomka J . Atherosclerotic plaque composition: analysis with multicolor CT and targeted gold nanoparticles. Radiology. 2010; 256(3):774-82. PMC: 2923725. DOI: 10.1148/radiol.10092473. View

13.

Ghaghada K, Badea C, Karumbaiah L, Fettig N, Bellamkonda R, Johnson G . Evaluation of tumor microenvironment in an animal model using a nanoparticle contrast agent in computed tomography imaging. Acad Radiol. 2010; 18(1):20-30. PMC: 3016875. DOI: 10.1016/j.acra.2010.09.003. View

14.

Perets N, Betzer O, Shapira R, Brenstein S, Angel A, Sadan T . Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neurodevelopmental Disorders. Nano Lett. 2019; 19(6):3422-3431. DOI: 10.1021/acs.nanolett.8b04148. View

15.

Velasco-Aguirre C, Morales-Zavala F, Salas-Huenuleo E, Gallardo-Toledo E, Andonie O, Munoz L . Improving gold nanorod delivery to the central nervous system by conjugation to the shuttle Angiopep-2. Nanomedicine (Lond). 2017; 12(20):2503-2517. DOI: 10.2217/nnm-2017-0181. View

16.

Xue D, Zhao M, Wang Y, Wang L, Yang Y, Wang S . A multifunctional peptide rescues memory deficits in Alzheimer's disease transgenic mice by inhibiting Aβ42-induced cytotoxicity and increasing microglial phagocytosis. Neurobiol Dis. 2012; 46(3):701-9. DOI: 10.1016/j.nbd.2012.03.013. View

17.

Morales-Zavala F, Arriagada H, Hassan N, Velasco C, Riveros A, Alvarez A . Peptide multifunctionalized gold nanorods decrease toxicity of β-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease. Nanomedicine. 2017; 13(7):2341-2350. DOI: 10.1016/j.nano.2017.06.013. View

18.

Betzer O, Perets N, Angel A, Motiei M, Sadan T, Yadid G . In Vivo Neuroimaging of Exosomes Using Gold Nanoparticles. ACS Nano. 2017; 11(11):10883-10893. DOI: 10.1021/acsnano.7b04495. View

19.

Garcia-Alloza M, Robbins E, Zhang-Nunes S, Purcell S, Betensky R, Raju S . Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol Dis. 2006; 24(3):516-24. DOI: 10.1016/j.nbd.2006.08.017. View

20.

van Groen T, Kadish I, Wiesehan K, Funke S, Willbold D . In vitro and in vivo staining characteristics of small, fluorescent, Abeta42-binding D-enantiomeric peptides in transgenic AD mouse models. ChemMedChem. 2008; 4(2):276-82. DOI: 10.1002/cmdc.200800289. View