Jacqmarcq Charlène, Picot Audrey, Flon Jules, Lebrun Florent, Martinez de Lizarrondo Sara, Naveau Mikaël, Bernay Benoît, Goux Didier, Rubio Marina, Malzert-Fréon Aurélie, Michel Anita, Proamer Fabienne, Mangin Pierre, Gauberti Maxime, Vivien Denis, Bonnard Thomas
Normandie University, UNICAEN, Université Caen Normandie, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institute Blood and Brain @ Caen-Normandie (BB@C), Caen, France.
Normandie University, UNICAEN, Université Caen Normandie, CNRS UMS 3408, Caen, France.
Nat Commun. 2024 Jun 13;15(1):5070. doi: 10.1038/s41467-024-49480-x.
In acute ischemic stroke, even when successful recanalization is obtained, downstream microcirculation may still be obstructed by microvascular thrombosis, which is associated with compromised brain reperfusion and cognitive decline. Identifying these microthrombi through non-invasive methods remains challenging. We developed the PHySIOMIC (Polydopamine Hybridized Self-assembled Iron Oxide Mussel Inspired Clusters), a MRI-based contrast agent that unmasks these microthrombi. In a mouse model of thromboembolic ischemic stroke, our findings demonstrate that the PHySIOMIC generate a distinct hypointense signal on T*-weighted MRI in the presence of microthrombi, that correlates with the lesion areas observed 24 hours post-stroke. Our microfluidic studies reveal the role of fibrinogen in the protein corona for the thrombosis targeting properties. Finally, we observe the biodegradation and biocompatibility of these particles. This work demonstrates that the PHySIOMIC particles offer an innovative and valuable tool for non-invasive in vivo diagnosis and monitoring of microthrombi, using MRI during ischemic stroke.
Nat Commun. 2024-6-13
Contrast Media Mol Imaging. 2009
Int J Nanomedicine. 2018-7-25
Int J Mol Sci. 2022-10-19
Stroke. 2019-10-10