The Development of Clioquinol Labeled-Gold Nanoparticles for the Treatment of Alzheimer’s Disease

Authors

  • Selice Jung Seoul Academy, Seoul, 06200, Republic of Korea
  • Jooyeong Lee Fayston Preparatory of Suji, Yongin, 16802, Republic of Korea

DOI:

https://doi.org/10.47577/biochemmed.v9i.11747

Keywords:

Alzheimer’s Disease, Amyloid-beta, Clioquinol, Gold Nanoparticles, Metal Chelation, Nanomedicine

Abstract

Clioquinol has emerged as a prominent metal-chelating agent for Alzheimer’s Disease. While clioquinol was once a popular antibiotic for skin infections, it has recently been investigated as a potential therapeutic for Alzheimer’s Disease. Its metal chelating property can restore metal homeostasis and prevent copper (Cu2+) and zinc (Zn2+) from interacting with amyloid-β (Aβ) peptides. Here, we propose labeling gold nanoparticles with clioquinol as a novel therapeutic approach for Alzheimer’s Disease to enable effective delivery of the agent across the blood-brain barrier. Based on previous studies on the individual efficacies of clioquinol and gold nanoparticles, we anticipate that this approach will prevent the formation of Aβ oligomers by disrupting metal-protein interactions. Our proposed clioquinol-labeled gold nanoparticles provide a novel curative approach for Alzheimer’s Disease and insights into subsequent therapeutic developments.

References

Alzheimer's Association. (2024). 2024 Alzheimer’s Disease Facts and Figures. Alzheimer’s & Dementia, 20(5). https://doi.org/10.1002/alz.13809

National Institute on Aging. (2024, July 2). What Causes Alzheimer’s Disease? National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-causes-alzheimers-disease

Centers for Disease Control and Prevention. (2023, April 12). About Alzheimer’s Disease | Aging. Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/aging/alzheimers-disease-dementia/about-alzheimers.html

Karran, E., Mercken, M., & De Strooper, B. (2011). The Amyloid Cascade Hypothesis for Alzheimer’s Disease: An Appraisal for the Development of Therapeutics. Nature Reviews Drug Discovery, 10(9), 698–712. https://doi.org/10.1038/nrd3505

Dai, X.-L., Sun, Y.-X., & Jiang, Z.-F. (2006). Cu(II) Potentiation of Alzheimer Aβ1-40 Cytotoxicity and Transition on its Secondary Structure. Acta Biochimica et Biophysica Sinica, 38(11), 765–772. https://doi.org/10.1111/j.1745-7270.2006.00228.x

Parthasarathy, S., Yoo, B., McElheny, D., Tay, W., & Ishii, Y. (2014). Capturing a Reactive State of Amyloid Aggregates. Journal of Biological Chemistry, 289(14), 9998–10010. https://doi.org/10.1074/jbc.m113.511345

Xie, Z., Wu, H., & Zhao, J. (2020). Multifunctional Roles of Zinc in Alzheimer’s Disease. NeuroToxicology, 80, 112–123. https://doi.org/10.1016/j.neuro.2020.07.003

Tramontin, N. dos S., da Silva, S., Arruda, R., Ugioni, K. S., Canteiro, P. B., de Bem Silveira, G., Mendes, C., Silveira, P. C. L., & Muller, A. P. (2019). Gold Nanoparticles Treatment Reverses Brain Damage in Alzheimer’s Disease Model. Molecular Neurobiology, 57(2), 926–936. https://doi.org/10.1007/s12035-019-01780-w

Bondiolotti, G., Sala, M., Pollera, C., Gervasoni, M., Puricelli, M., Ponti, W., & Bareggi, S. R. (2010). Pharmacokinetics and Distribution of Clioquinol in Golden Hamsters. Journal of Pharmacy and Pharmacology, 59(3), 387–393. https://doi.org/10.1211/jpp.59.3.0008

National Institute on Aging. (2023a, September 12). How is Alzheimer’s Disease Treated? National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-treatment/how-alzheimers-disease-treated

Das, S., & Bharati, K. (2023). Recent Advances in Treatment of Alzheimer’s Disease. International Journal of Alzheimer’s Disease Research, 1(2), 34–38. https://www.opastpublishers.com/open-access-articles/recent-advances-in-treatment-of-alzheimers-disease.pdf

Bagheri, S., Squitti, R., Haertlé, T., Siotto, M., & Saboury, A. A. (2018). Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals. Frontiers in Aging Neuroscience, 9. https://doi.org/10.3389/fnagi.2017.00446

Bareggi, S. R., & Cornelli, U. (2010). Clioquinol: Review of Its Mechanisms of Action and Clinical Uses in Neurodegenerative Disorders. CNS Neuroscience & Therapeutics, 18(1), 41–46. https://doi.org/10.1111/j.1755-5949.2010.00231.x

Ritchie, C. W., Bush, A. I., Mackinnon, A., Macfarlane, S., Mastwyk, M., MacGregor, L., Kiers, L., Cherny, R., Li, Q.-X., Tammer, A., Carrington, D., Mavros, C., Volitakis, I., Xilinas, M., Ames, D., Davis, S., Beyreuther, K., Tanzi, R. E., & Masters, C. L. (2003). Metal-Protein Attenuation With Iodochlorhydroxyquin (Clioquinol) Targeting Aβ Amyloid Deposition and Toxicity in Alzheimer Disease. Archives of Neurology, 60(12), 1685. https://doi.org/10.1001/archneur.60.12.1685

Treiber, C., Simons, A., Strauss, M., Hafner, M., Cappai, R., Bayer, T. A., & Multhaup, G. (2004). Clioquinol Mediates Copper Uptake and Counteracts Copper Efflux Activities of the Amyloid Precursor Protein of Alzheimer’s Disease. Journal of Biological Chemistry, 279(50), 51958–51964. https://doi.org/10.1074/jbc.m407410200

Kimura, E., Hirano, T., Yamashita, S., Hirai, T., Uchida, Y., Maeda, Y., & Uchino, M. (2011). Cervical MRI of Subacute Myelo-Optico-Neuropathy. Spinal Cord, 49(2), 182–185. https://doi.org/10.1038/sc.2010.68

Mao, X., & Schimmer, A. D. (2008). The Toxicology of Clioquinol. Toxicology Letters, 182(1-3), 1–6. https://doi.org/10.1016/j.toxlet.2008.08.015

Bors, L. A., & Erdő, F. (2019). Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery. Scientia Pharmaceutica, 87(1), 6. https://doi.org/10.3390/scipharm87010006

Sokolova, V., Nzou, G., van der Meer, S. B., Ruks, T., Heggen, M., Loza, K., Hagemann, N., Murke, F., Giebel, B., Hermann, D. M., Atala, A. J., & Epple, M. (2020). Ultrasmall Gold Nanoparticles (2 nm) Can Penetrate and Enter Cell Nuclei in an in Vitro 3D Brain Spheroid Model. Acta Biomaterialia, 111, 349–362. https://doi.org/10.1016/j.actbio.2020.04.023

Mudshinge, S. R., Deore, A. B., Patil, S., & Bhalgat, C. M. (2011). Nanoparticles: Emerging Carriers for Drug Delivery. Saudi Pharmaceutical Journal, 19(3), 129–141. https://doi.org/10.1016/j.jsps.2011.04.001

Amina, S. J., & Guo, B. (2020). A Review on the Synthesis and Functionalization of Gold Nanoparticles as a Drug Delivery Vehicle. International Journal of Nanomedicine, 15, 9823–9857. https://doi.org/10.2147/ijn.s279094

Yeh, Y.-C., Creran, B., & Rotello, V. M. (2011). Gold Nanoparticles: Preparation, Properties, and Applications in Bionanotechnology. Nanoscale, 4(6), 1871–1880. https://doi.org/10.1039/c1nr11188d

Bürgi, T. (2015). Properties of the Gold–Sulphur Interface: From Self-Assembled Monolayers to Clusters. Nanoscale, 7(38), 15553–15567. https://doi.org/10.1039/C5NR03497C

Scantox. (n.d.). Tg2576 Transgenic Mouse Model. Scantox. https://scantox.com/services/discovery/animal-models/alzheimers-disease-transgenic-mouse-models/tg2576-mouse-model/

Wilschefski, S. C., & Baxter, M. R. (2019). Inductively Coupled Plasma Mass Spectrometry: Introduction to Analytical Aspects. Clinical Biochemist Reviews, 40(3), 115–133. https://doi.org/10.33176/aacb-19-00024 [26] Iscen, A., Brue, C. R., Roberts, K. F., Kim, J., Schatz, G. C., & Meade, T. J. (2019). Inhibition of Amyloid-β Aggregation by Cobalt(III) Schiff Base Complexes: A Computational and Experimental Approach. Journal of the American Chemical Society, 141(42), 16685–16695. https://doi.org/10.1021/jacs.9b06388

Chan, T. G., Ruehl, C. L., Morse, S. V., Simon, M., Rakers, V., Watts, H., Aprile, F. A., Choi, J. J., & Vilar, R. (2021). Modulation of Amyloid-β Aggregation by Metal Complexes With a Dual Binding Mode and Their Delivery Across the Blood–Brain Barrier Using Focused Ultrasound. Chemical Science, 12(27), 9485–9493. https://doi.org/10.1039/d1sc02273c

Melich, R., Valour, J.-P., Urbaniak, S., Padilla, F., & Charcosset, C. (2019). Preparation and Characterization of Perfluorocarbon Microbubbles Using Shirasu Porous Glass (SPG) Membranes. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 560, 233–243. https://doi.org/10.1016/j.colsurfa.2018.09.058

Maksimova, E. A., Barmin, R. A., Rudakovskaya, P. G., Sindeeva, O. A., Prikhozhdenko, E. S., Yashchenok, A. M., Khlebtsov, B. N., Solovev, A. A., Huang, G., Mei, Y., Dey, K. K., & Gorin, D. A. (2021). Air-Filled Microbubbles Based on Albumin Functionalized with Gold Nanocages and Zinc Phthalocyanine for Multimodal Imaging. Micromachines, 12(10), 1161. https://doi.org/10.3390/mi12101161

Borrelli, M. J., O’Brien, W. D., Bernock, L. J., Williams, H. R., Hamilton, E., Wu, J., Oelze, M. L., & Culp, W. C. (2012). Production of Uniformly Sized Serum Albumin and Dextrose Microbubbles. Ultrasonics Sonochemistry, 19(1), 198–208. https://doi.org/10.1016/j.ultsonch.2011.05.010

Singh, A., Sharma, A., & Chawla, P. A. (2023). The Catalyst’s Companion: N,N′-Dicyclohexylcarbodiimide (DCC) in Action. SynOpen, 07(04), 562–565. https://doi.org/10.1055/s-0042-1751500

Visikol. (n.d.). Visikol’s Unique Blood Brain Barrier Assay. Visikol | BICO Company. https://visikol.com/blog/2024/02/13/visikols-unique-blood-brain-barrier-assay/

Hanada, S., Fujioka, K., Inoue, Y., Kanaya, F., Manome, Y., & Yamamoto, K. (2014). Cell-Based in Vitro Blood-Brain Barrier Model Can Rapidly Evaluate Nanoparticles’ Brain Permeability in Association with Particle Size and Surface Modification. International Journal of Molecular Sciences, 15(2), 1812–1825. https://doi.org/10.3390/ijms15021812

Sela, H., Cohen, H., Elia, P., Zach, R., Karpas, Z., & Zeiri, Y. (2015). Spontaneous Penetration of Gold Nanoparticles Through the Blood Brain Barrier (BBB). Journal of Nanobiotechnology, 13(1). https://doi.org/10.1186/s12951-015-0133-1

Song, X., Chen, J., Hou, Z., & Xie, N. (2021). Antimicrobial Therapy and the Potential Mechanisms in Alzheimer’s Disease. Neuroscience Letters, 741, 135464. https://doi.org/10.1016/j.neulet.2020.135464

Li, C., Wang, J., & Zhou, B. (2010). The Metal Chelating and Chaperoning Effects of Clioquinol: Insights from Yeast Studies. Journal of Alzheimer’s Disease, 21(4), 1249–1262. https://doi.org/10.3233/jad-2010-100024

Benvenisti-Zarom, L., Chen, J., & Regan, R. F. (2005). The Oxidative Neurotoxicity of Clioquinol. Neuropharmacology, 49(5), 687–694. https://doi.org/10.1016/j.neuropharm.2005.04.023

Gros, L., Ishchenko, A. A., & Saparbaev, M. (2003). Enzymology of Repair of Etheno-Adducts. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 531(1-2), 219–229. https://doi.org/10.1016/j.mrfmmm.2003.07.008

Lin, G., Zhu, F., Kanaan, N. M., Asano, R., Shirafuji, N., Sasaki, H., Yamaguchi, T., Enomoto, S., Endo, Y., Ueno, A., Ikawa, M., Hayashi, K., Yamamura, O., Yen, S.-H., Nakamoto, Y., & Hamano, T. (2021). Clioquinol Decreases Levels of Phosphorylated, Truncated, and Oligomerized Tau Protein. International Journal of Molecular Sciences, 22(21), 12063. https://doi.org/10.3390/ijms222112063

Grossi, C., Francese, S., Casini, A., Rosi, M. C., Luccarini, I., Fiorentini, A., Gabbiani, C., Messori, L., Moneti, G., & Casamenti, F. (2009). Clioquinol Decreases Amyloid-β Burden and Reduces Working Memory Impairment in a Transgenic Mouse Model of Alzheimer’s Disease. Journal of Alzheimer’s Disease, 17(2), 423–440. https://doi.org/10.3233/jad-2009-1063

Alzheimer's Impact Movement. (2024, March 21). Congress Reaches Bipartisan Agreement on $100 Million Alzheimer’s Research Funding Increase and Continued Investment in Alzheimer’s Public Health Infrastructure. Alzheimer’s Impact Movement. https://alzimpact.org/Congress-Reaches-Bipartisan-Agreement-on-%24100-Million-Research-Funding-Increase

National Institute on Aging. (2023b, March 1). Alzheimer’s Disease Genetics Fact Sheet. National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/alzheimers-disease-genetics-fact-sheet

Mayo Clinic. (2023, April 29). Alzheimer’s Genes: Are You at Risk? Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-genes/art-20046552

Jureschi, M., Lupaescu, A. V., Ion, L., Petre, B. A., & Drochioiu, G. (2019). Stoichiometry of Heavy Metal Binding to Peptides Involved in Alzheimer’s Disease: Mass Spectrometric Evidence. Advancements of Mass Spectrometry in Biomedical Research, 1140, 401–415. https://doi.org/10.1007/978-3-030-15950-4_23

National Center for Biotechnology Information. (n.d.). PubChem Compound Summary for CID 2788, Clioquinol. National Institutes of Health. https://pubchem.ncbi.nlm.nih.gov/compound//2788#section= 2D-Structure

Downloads

Published

2024-09-25

How to Cite

Jung, S., & Lee, J. (2024). The Development of Clioquinol Labeled-Gold Nanoparticles for the Treatment of Alzheimer’s Disease. Technium BioChemMed, 9, 48–56. https://doi.org/10.47577/biochemmed.v9i.11747