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A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis

Atherosclerosis is at the onset of the cardiovascular diseases that are among the leading causes of death worldwide. Currently, high-risk plaques, also called vulnerable atheromatous plaques, remain often undiagnosed until the occurrence of severe complications, such as stroke or myocardial infarcti...

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Autores principales: Bonnet, Samuel, Prévot, Geoffrey, Mornet, Stéphane, Jacobin-Valat, Marie-Josée, Mousli, Yannick, Hemadou, Audrey, Duttine, Mathieu, Trotier, Aurélien, Sanchez, Stéphane, Duonor-Cérutti, Martine, Crauste-Manciet, Sylvie, Clofent-Sanchez, Gisèle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153629/
https://www.ncbi.nlm.nih.gov/pubmed/34068875
http://dx.doi.org/10.3390/ijms22105188
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author Bonnet, Samuel
Prévot, Geoffrey
Mornet, Stéphane
Jacobin-Valat, Marie-Josée
Mousli, Yannick
Hemadou, Audrey
Duttine, Mathieu
Trotier, Aurélien
Sanchez, Stéphane
Duonor-Cérutti, Martine
Crauste-Manciet, Sylvie
Clofent-Sanchez, Gisèle
author_facet Bonnet, Samuel
Prévot, Geoffrey
Mornet, Stéphane
Jacobin-Valat, Marie-Josée
Mousli, Yannick
Hemadou, Audrey
Duttine, Mathieu
Trotier, Aurélien
Sanchez, Stéphane
Duonor-Cérutti, Martine
Crauste-Manciet, Sylvie
Clofent-Sanchez, Gisèle
author_sort Bonnet, Samuel
collection PubMed
description Atherosclerosis is at the onset of the cardiovascular diseases that are among the leading causes of death worldwide. Currently, high-risk plaques, also called vulnerable atheromatous plaques, remain often undiagnosed until the occurrence of severe complications, such as stroke or myocardial infarction. Molecular imaging agents that target high-risk atheromatous lesions could greatly improve the diagnosis of atherosclerosis by identifying sites of high disease activity. Moreover, a “theranostic approach” that combines molecular imaging agents (for diagnosis) and therapeutic molecules would be of great value for the local management of atheromatous plaques. The aim of this study was to develop and characterize an innovative theranostic tool for atherosclerosis. We engineered oil-in-water nano-emulsions (NEs) loaded with superparamagnetic iron oxide (SPIO) nanoparticles for magnetic resonance imaging (MRI) purposes. Dynamic MRI showed that NE-SPIO nanoparticles decorated with a polyethylene glycol (PEG) layer reduced their liver uptake and extended their half-life. Next, the NE-SPIO-PEG formulation was functionalized with a fully human scFv-Fc antibody (P3) recognizing galectin 3, an atherosclerosis biomarker. The P3-functionalized formulation targeted atheromatous plaques, as demonstrated in an immunohistochemistry analyses of mouse aorta and human artery sections and in an Apoe(−/−) mouse model of atherosclerosis. Moreover, the formulation was loaded with SPIO nanoparticles and/or alpha-tocopherol to be used as a theranostic tool for atherosclerosis imaging (SPIO) and for delivery of drugs that reduce oxidation (here, alpha-tocopherol) in atheromatous plaques. This study paves the way to non-invasive targeted imaging of atherosclerosis and synergistic therapeutic applications.
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spelling pubmed-81536292021-05-27 A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis Bonnet, Samuel Prévot, Geoffrey Mornet, Stéphane Jacobin-Valat, Marie-Josée Mousli, Yannick Hemadou, Audrey Duttine, Mathieu Trotier, Aurélien Sanchez, Stéphane Duonor-Cérutti, Martine Crauste-Manciet, Sylvie Clofent-Sanchez, Gisèle Int J Mol Sci Article Atherosclerosis is at the onset of the cardiovascular diseases that are among the leading causes of death worldwide. Currently, high-risk plaques, also called vulnerable atheromatous plaques, remain often undiagnosed until the occurrence of severe complications, such as stroke or myocardial infarction. Molecular imaging agents that target high-risk atheromatous lesions could greatly improve the diagnosis of atherosclerosis by identifying sites of high disease activity. Moreover, a “theranostic approach” that combines molecular imaging agents (for diagnosis) and therapeutic molecules would be of great value for the local management of atheromatous plaques. The aim of this study was to develop and characterize an innovative theranostic tool for atherosclerosis. We engineered oil-in-water nano-emulsions (NEs) loaded with superparamagnetic iron oxide (SPIO) nanoparticles for magnetic resonance imaging (MRI) purposes. Dynamic MRI showed that NE-SPIO nanoparticles decorated with a polyethylene glycol (PEG) layer reduced their liver uptake and extended their half-life. Next, the NE-SPIO-PEG formulation was functionalized with a fully human scFv-Fc antibody (P3) recognizing galectin 3, an atherosclerosis biomarker. The P3-functionalized formulation targeted atheromatous plaques, as demonstrated in an immunohistochemistry analyses of mouse aorta and human artery sections and in an Apoe(−/−) mouse model of atherosclerosis. Moreover, the formulation was loaded with SPIO nanoparticles and/or alpha-tocopherol to be used as a theranostic tool for atherosclerosis imaging (SPIO) and for delivery of drugs that reduce oxidation (here, alpha-tocopherol) in atheromatous plaques. This study paves the way to non-invasive targeted imaging of atherosclerosis and synergistic therapeutic applications. MDPI 2021-05-14 /pmc/articles/PMC8153629/ /pubmed/34068875 http://dx.doi.org/10.3390/ijms22105188 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bonnet, Samuel
Prévot, Geoffrey
Mornet, Stéphane
Jacobin-Valat, Marie-Josée
Mousli, Yannick
Hemadou, Audrey
Duttine, Mathieu
Trotier, Aurélien
Sanchez, Stéphane
Duonor-Cérutti, Martine
Crauste-Manciet, Sylvie
Clofent-Sanchez, Gisèle
A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis
title A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis
title_full A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis
title_fullStr A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis
title_full_unstemmed A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis
title_short A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis
title_sort nano-emulsion platform functionalized with a fully human scfv-fc antibody for atheroma targeting: towards a theranostic approach to atherosclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153629/
https://www.ncbi.nlm.nih.gov/pubmed/34068875
http://dx.doi.org/10.3390/ijms22105188
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