TY - JOUR
T1 - Functionalization of stable fluorescent nanodiamonds towards reliable detection of biomarkers for Alzheimer's disease
AU - Morales-Zavala, Francisco
AU - Casanova-Morales, Nathalie
AU - Gonzalez, Raúl B.
AU - Chandía-Cristi, América
AU - Estrada, Lisbell D.
AU - Alvizú, Ignacio
AU - Waselowski, Victor
AU - Guzman, Fanny
AU - Guerrero, Simón
AU - Oyarzún-Olave, Marisol
AU - Rebolledo, Cristian
AU - Rodriguez, Enrique
AU - Armijo, Julien
AU - Bhuyan, Heman
AU - Favre, Mario
AU - Alvarez, Alejandra R.
AU - Kogan, Marcelo J.
AU - Maze, Jerónimo R.
N1 - Funding Information:
The authors acknowledge support from Conicyt‑PIA program grant ACT1108 and Conicyt‑Fondequip grant EQM140168. ACC acknowledges support from Beca Doctorado Nacional 21120617. MK acknowledges Fondap 15130011 and Fondecyt 1170929. JRM acknowledges support from Conicyt‑Fondecyt program grant 1141185, 1180673 and AFOSR grant FA9550‑15‑1‑0113 and FA9550‑16‑1‑0384. JA acknowledges support from Fondecyt grant 3150587. ARA acknowledges support from Fondecyt grant 1161065, Basal Funding CONICYT‑AFB‑170005 (CARE) and FONDEF D10E1077.
Funding Information:
Conicyt‑PIA program grant No ACT1108. ACC acknowledges support from Beca Doctorado Nacional 21120617. MK acknowledges to Fondap 15130011 and Fondecyt 1130425. JRM acknowledges support from Conicyt‑Fondecyt program grant No 1141185, No 1180673, and AFOSR grant No FA9550‑15‑1‑ 0113 and FA9550‑16‑1‑0384. JA acknowledges support from Fondecyt grant 3150587. ARA acknowledges support from Fondecyt grant 1161065 and Basal Funding CONICYT‑PFB‑12/2007 (CARE).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/8/10
Y1 - 2018/8/10
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Amyloid beta peptide
KW - Fluorescent markers
KW - Nanodiamonds
KW - Peptide R7-CLPFFD
UR - http://www.scopus.com/inward/record.url?scp=85051538804&partnerID=8YFLogxK
U2 - 10.1186/s12951-018-0385-7
DO - 10.1186/s12951-018-0385-7
M3 - Article
C2 - 30097010
AN - SCOPUS:85051538804
SN - 1477-3155
VL - 16
JO - Journal of Nanobiotechnology
JF - Journal of Nanobiotechnology
IS - 1
M1 - 60
ER -