Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimer’s disease

Abstract Background Stable and non-toxic fluorescent markers are gaining attention in molecular diagnostics as powerful tools for enabling long and reliable biological studies. Such markers should not only have a long half-life under several assay conditions showing no photo bleaching or blinking bu...

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Main Authors: Francisco Morales-Zavala, Nathalie Casanova-Morales, Raúl B. Gonzalez, América Chandía-Cristi, Lisbell D. Estrada, Ignacio Alvizú, Victor Waselowski, Fanny Guzman, Simón Guerrero, Marisol Oyarzún-Olave, Cristian Rebolledo, Enrique Rodriguez, Julien Armijo, Heman Bhuyan, Mario Favre, Alejandra R. Alvarez, Marcelo J. Kogan, Jerónimo R. Maze
Format: Article
Language:English
Published: BMC 2018-08-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12951-018-0385-7
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author Francisco Morales-Zavala
Nathalie Casanova-Morales
Raúl B. Gonzalez
América Chandía-Cristi
Lisbell D. Estrada
Ignacio Alvizú
Victor Waselowski
Fanny Guzman
Simón Guerrero
Marisol Oyarzún-Olave
Cristian Rebolledo
Enrique Rodriguez
Julien Armijo
Heman Bhuyan
Mario Favre
Alejandra R. Alvarez
Marcelo J. Kogan
Jerónimo R. Maze
author_facet Francisco Morales-Zavala
Nathalie Casanova-Morales
Raúl B. Gonzalez
América Chandía-Cristi
Lisbell D. Estrada
Ignacio Alvizú
Victor Waselowski
Fanny Guzman
Simón Guerrero
Marisol Oyarzún-Olave
Cristian Rebolledo
Enrique Rodriguez
Julien Armijo
Heman Bhuyan
Mario Favre
Alejandra R. Alvarez
Marcelo J. Kogan
Jerónimo R. Maze
author_sort Francisco Morales-Zavala
collection DOAJ
description Abstract Background Stable and non-toxic fluorescent markers are gaining attention in molecular diagnostics as powerful tools for enabling long and reliable biological studies. Such markers should not only have a long half-life under several assay conditions showing no photo bleaching or blinking but also, they must allow for their conjugation or functionalization as a crucial step for numerous applications such as cellular tracking, biomarker detection and drug delivery. Results We report the functionalization of stable fluorescent markers based on nanodiamonds (NDs) with a bifunctional peptide. This peptide is made of a cell penetrating peptide and a six amino acids long β-sheet breaker peptide that is able to recognize amyloid β (Aβ) aggregates, a biomarker for the Alzheimer disease. Our results indicate that functionalized NDs (fNDs) are not cytotoxic and can be internalized by the cells. The fNDs allow ultrasensitive detection (at picomolar concentrations of NDs) of in vitro amyloid fibrils and amyloid aggregates in AD mice brains. Conclusions The fluorescence of functionalized NDs is more stable than that of fluorescent markers commonly used to stain Aβ aggregates such as Thioflavin T. These results pave the way for performing ultrasensitive and reliable detection of Aβ aggregates involved in the pathogenesis of the Alzheimer disease.
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spelling doaj.art-d5d9948034a34eb69432812892a2904a2022-12-22T02:21:30ZengBMCJournal of Nanobiotechnology1477-31552018-08-0116111410.1186/s12951-018-0385-7Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimer’s diseaseFrancisco Morales-Zavala0Nathalie Casanova-Morales1Raúl B. Gonzalez2América Chandía-Cristi3Lisbell D. Estrada4Ignacio Alvizú5Victor Waselowski6Fanny Guzman7Simón Guerrero8Marisol Oyarzún-Olave9Cristian Rebolledo10Enrique Rodriguez11Julien Armijo12Heman Bhuyan13Mario Favre14Alejandra R. Alvarez15Marcelo J. Kogan16Jerónimo R. Maze17Department of Pharmacological and Toxicological Chemistry, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de ChileInstitute of Physics, Pontificia Universidad Católica de ChileInstitute of Physics, Pontificia Universidad Católica de ChileDepartment of Cellular & Molecular Biology, Pontificia Universidad Católica de ChileCIBQA, Universidad Bernardo O’HigginsInstitute of Physics, Pontificia Universidad Católica de ChileInstitute of Physics, Pontificia Universidad Católica de ChileNúcleo de Biotecnología Curauma, Pontificia Universidad Católica de ValparaísoDepartment of Pharmacological and Toxicological Chemistry, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de ChileDepartment of Cellular & Molecular Biology, Pontificia Universidad Católica de ChileInstitute of Physics, Pontificia Universidad Católica de ChileInstitute of Physics, Pontificia Universidad Católica de ChileInstitute of Physics, Pontificia Universidad Católica de ChileInstitute of Physics, Pontificia Universidad Católica de ChileInstitute of Physics, Pontificia Universidad Católica de ChileDepartment of Cellular & Molecular Biology, Pontificia Universidad Católica de ChileDepartment of Pharmacological and Toxicological Chemistry, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de ChileInstitute of Physics, Pontificia Universidad Católica de ChileAbstract Background Stable and non-toxic fluorescent markers are gaining attention in molecular diagnostics as powerful tools for enabling long and reliable biological studies. Such markers should not only have a long half-life under several assay conditions showing no photo bleaching or blinking but also, they must allow for their conjugation or functionalization as a crucial step for numerous applications such as cellular tracking, biomarker detection and drug delivery. Results We report the functionalization of stable fluorescent markers based on nanodiamonds (NDs) with a bifunctional peptide. This peptide is made of a cell penetrating peptide and a six amino acids long β-sheet breaker peptide that is able to recognize amyloid β (Aβ) aggregates, a biomarker for the Alzheimer disease. Our results indicate that functionalized NDs (fNDs) are not cytotoxic and can be internalized by the cells. The fNDs allow ultrasensitive detection (at picomolar concentrations of NDs) of in vitro amyloid fibrils and amyloid aggregates in AD mice brains. Conclusions The fluorescence of functionalized NDs is more stable than that of fluorescent markers commonly used to stain Aβ aggregates such as Thioflavin T. These results pave the way for performing ultrasensitive and reliable detection of Aβ aggregates involved in the pathogenesis of the Alzheimer disease.http://link.springer.com/article/10.1186/s12951-018-0385-7Fluorescent markersNanodiamondsPeptide R7-CLPFFDAlzheimer’s diseaseAmyloid beta peptide
spellingShingle Francisco Morales-Zavala
Nathalie Casanova-Morales
Raúl B. Gonzalez
América Chandía-Cristi
Lisbell D. Estrada
Ignacio Alvizú
Victor Waselowski
Fanny Guzman
Simón Guerrero
Marisol Oyarzún-Olave
Cristian Rebolledo
Enrique Rodriguez
Julien Armijo
Heman Bhuyan
Mario Favre
Alejandra R. Alvarez
Marcelo J. Kogan
Jerónimo R. Maze
Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimer’s disease
Journal of Nanobiotechnology
Fluorescent markers
Nanodiamonds
Peptide R7-CLPFFD
Alzheimer’s disease
Amyloid beta peptide
title Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimer’s disease
title_full Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimer’s disease
title_fullStr Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimer’s disease
title_full_unstemmed Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimer’s disease
title_short Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimer’s disease
title_sort functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for alzheimer s disease
topic Fluorescent markers
Nanodiamonds
Peptide R7-CLPFFD
Alzheimer’s disease
Amyloid beta peptide
url http://link.springer.com/article/10.1186/s12951-018-0385-7
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