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Nanomedicine. 2017 Oct;13(7):2341-2350. doi: 10.1016/j.nano.2017.06.013. Epub 2017 Jun 30.

Peptide multifunctionalized gold nanorods decrease toxicity of β-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease.

Author information

1
Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Independencia, Santiago, Chile. Electronic address: pancho.morales@gmail.com.
2
Escuela de Biotecnología, Facultad de Ciencias, Universidad Santo Tomás, Ejercito 146, Santiago, Chile. Electronic address: hector.arriagada@usach.cl.
3
Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago; Programa Institucional de Fomento a la I+D+I, Universidad Tecnológica Metropolitana, Edificio de Ciencia y Tecnologia, Ignacio Valdivieso 2409, San Joaquin. Electronic address: nhassan@utem.cl.
4
Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Independencia, Santiago, Chile. Electronic address: carolinavelasco@ug.uchile.cl.
5
Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Independencia, Santiago, Chile. Electronic address: riveros.ana@gmail.com.
6
Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago 8331010, Chile; Centro de envejecimiento y regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: aalvarez@bio.puc.cl.
7
Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago 8331010, Chile. Electronic address: aminniti@bio.puc.cl.
8
Sección de Metrología Química, Comisión Chilena de Energía Nuclear, Nueva Bilbao 12501, La Reina, Santiago, Chile. Electronic address: xrojas@cchen.cl.
9
Sección de Metrología Química, Comisión Chilena de Energía Nuclear, Nueva Bilbao 12501, La Reina, Santiago, Chile. Electronic address: lmunoz@cchen.cl.
10
Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Independencia, Santiago, Chile; Departamento de Ciencias Quimicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Av. Republica 275, Santiago, Chile. Electronic address: rvasquez1982@gmail.com.
11
Departamento de Ciencias Quimicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Av. Republica 275, Santiago, Chile. Electronic address: katherinerd24@gmail.com.
12
Institute for Research in Biomedicine-Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain. Electronic address: macarena.sanchez@irbbarcelona.org.
13
Institute for Research in Biomedicine-Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain. Electronic address: ernest.giralt@irbbarcelona.org.
14
Departamento de Ciencias Quimicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Av. Republica 275, Santiago, Chile. Electronic address: eyleen.araya@unab.cl.
15
Escuela de Biotecnología, Facultad de Ciencias, Universidad Santo Tomás, Ejercito 146, Santiago, Chile. Electronic address: rebecaaldunatem@gmail.com.
16
Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Independencia, Santiago, Chile. Electronic address: mkogan@ciq.uchile.cl.

Abstract

The properties of nanometric materials make nanotechnology a promising platform for tackling problems of contemporary medicine. In this work, gold nanorods were synthetized and stabilized with polyethylene glycols and modified with two kinds of peptides. The D1 peptide that recognizes toxic aggregates of Aβ, a peptide involved in Alzheimer's disease (AD); and the Angiopep 2 that can be used to deliver nanorods to the mammalian central nervous system. The nanoconjugates were characterized using absorption spectrophotometry, dynamic light scattering, and transmission electron microscopy, among other techniques. We determined that the nanoconjugate does not affect neuronal viability; it penetrates the cells, and decreases aggregation of Aβ peptide in vitro. We also showed that when we apply our nanosystem to a Caenorhabditis elegans AD model, the toxicity of aggregated Aβ peptide is decreased. This work may contribute to the development of therapies for AD based on metallic nanoparticles.

KEYWORDS:

Alzheimer's nanotherapy; Amyloid-beta-peptide; Drug-delivery; Gold-nanoparticle; Gold-nanorods

PMID:
28673851
DOI:
10.1016/j.nano.2017.06.013
[Indexed for MEDLINE]

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