Tracking the immune response by MRI using biodegradable and ultrasensitive microprobes

Author:

Martinez de Lizarrondo Sara1ORCID,Jacqmarcq Charlene1ORCID,Naveau Mikael2ORCID,Navarro-Oviedo Manuel1ORCID,Pedron Swannie1ORCID,Adam Alexandre3ORCID,Freis Barbara3ORCID,Allouche Stephane4ORCID,Goux Didier5ORCID,Razafindrakoto Sarah6,Gazeau Florence6,Mertz Damien3ORCID,Vivien Denis17ORCID,Bonnard Thomas1ORCID,Gauberti Maxime18ORCID

Affiliation:

1. Normandie Université, UNICAEN, INSERM, PhIND (Physiopathology and Imaging of Neurological Disorders), Institut Blood and Brain @ Caen-Normandie, Cyceron, 14000 Caen, France.

2. Normandie Université, UMS 3408 Cyceron, CNRS, University of Caen Normandy, GIP CYCERON, Caen, France.

3. Institut de Physique et de Chimie des Matériaux de Strasbourg (IPCMS), UMR-7504 CNRS—Université de Strasbourg, 23 rue du Lœss, 67034 Strasbourg, France.

4. CHU Caen, Department of Biochemistry, CHU de Caen Côte de Nacre, Caen, France.

5. Centre de Microscopie Appliquée à la Biologie (CMAbio), UniCaen, Normandie University, SF4206 Icore, 14000 Caen, France.

6. MSC, Université de Paris CNRS, UMR7057, 45 rue des Saints Pères 75006, Paris, France.

7. CHU Caen, Clinical Research Department, CHU de Caen Côte de Nacre, Caen, France.

8. CHU Caen, Department of Diagnostic Imaging and Interventional Radiology, CHU de Caen Côte de Nacre, Caen, France.

Abstract

Molecular magnetic resonance imaging (MRI) holds great promise for diagnosis and therapeutic monitoring in a wide range of diseases. However, the low intrinsic sensitivity of MRI to detect exogenous contrast agents and the lack of biodegradable microprobes have prevented its clinical development. Here, we synthetized a contrast agent for molecular MRI based on a previously unknown mechanism of self-assembly of catechol-coated magnetite nanocrystals into microsized matrix-based particles. The resulting biodegradable microprobes (M3P for microsized matrix-based magnetic particles) carry up to 40,000 times higher amounts of superparamagnetic material than classically used nanoparticles while preserving favorable biocompatibility and excellent water dispersibility. After conjugation to monoclonal antibodies, targeted M3P display high sensitivity and specificity to detect inflammation in vivo in the brain, kidneys, and intestinal mucosa. The high payload of superparamagnetic material, excellent toxicity profile, short circulation half-life, and widespread reactivity of the M3P particles provides a promising platform for clinical translation of immuno-MRI.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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