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

07 July 2021 par Super Administrateur [TheChamp-Sharing]
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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
by Samuel Bonnet

Lien vers l’article :

https://www.mdpi.com/1422-0067/22/10/5188

1,2,*,† [OrcID] , Geoffrey Prévot
3,† [OrcID] , Stéphane Mornet
2 [OrcID] , Marie-Josée Jacobin-Valat
1, Yannick Mousli
3, Audrey Hemadou
1, Mathieu Duttine
2 [OrcID] , Aurélien Trotier
1 [OrcID] , Stéphane Sanchez
1, Martine Duonor-Cérutti
4, Sylvie Crauste-Manciet
3,† [OrcID] and Gisèle Clofent-Sanchez
1,†
1
Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université de Bordeaux, CRMSB, 33076 Bordeaux, France
2
Institut de Chimie de la Matière Condensée, CNRS UMR 5026, Université de Bordeaux, Bordeaux INP, ICMCB, 33600 Pessac, France
3
ARNA, ARN, Régulations Naturelle et Artificielle, ChemBioPharm, INSERM U1212, CNRS UMR 5320, Université de Bordeaux, 33076 Bordeaux, France
4
CNRS UPS 3044, Baculovirus et Thérapie, 30380 Saint-Christol-lès-Alès, France
*
Author to whom correspondence should be addressed.

These authors contributed equally.
Academic Editors: Annamaria Sandomenico and Menotti Ruvo
Int. J. Mol. Sci. 2021, 22(10), 5188; https://doi.org/10.3390/ijms22105188
Received: 25 March 2021 / Revised: 8 May 2021 / Accepted: 9 May 2021 / Published: 14 May 2021
(This article belongs to the Special Issue Monoclonal Antibodies and Their Functional Fragments in Research, Diagnosis and Therapy 2.0)
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Abstract
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. View Full-Text
Keywords: atherosclerosis; nano-emulsion; magnetic resonance imaging; stealth; human antibody

 

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