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Molecules 2019, 24(5), 962; https://doi.org/10.3390/molecules24050962

Bimodal Fucoidan-Coated Zinc Oxide/Iron Oxide-Based Nanoparticles for the Imaging of Atherothrombosis

1
Laboratory for Vascular Translational Science, Inserm U1148, Institut Galilée—Université Paris Diderot, Université Paris 13, Sorbonne-Paris-Cité, 99 av JB Clément, 93430 Villetaneuse, France
2
Laboratoire de Physique des Lasers, UMR CNRS 7538, Institut Galilée—Université Paris 13, Sorbonne-Paris-Cité, 99 av JB Clément, 93430 Villetaneuse, France
3
Laboratoire des Sciences des Procédés et des Matériaux, UPR CNRS 3407, Institut Galilée—Université Paris 13, Sorbonne-Paris-Cité, 99 av JB Clément, 93430 Villetaneuse, France
4
Service de Médecine Nucléaire, Hôpital Avicenne Assistance Publique-Hôpitaux de Paris, F-93009 Bobigny, France
5
Laboratoire Phénix, UMR 8234, UPMC, 4 place Jussieu, 75252 Paris Cedex 05, France
6
Fédération de Recherche en Imagerie multimodalité (FRIM), UMS 34, Hôpital Bichat, 46 rue Henri Huchard, 75018 Paris Cedex, France
7
Université de Technologie de Compiègne, Service d’Analyse Physico-Chimique, Direction à la Recherche, Rue du Dr Schweitzer, CS 60319, 60203 Compiègne cedex, France
*
Author to whom correspondence should be addressed.
Received: 2 February 2019 / Revised: 3 March 2019 / Accepted: 6 March 2019 / Published: 8 March 2019
(This article belongs to the Special Issue Cardiovascular Nanomedicines and Nanomaterials )
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Abstract

A polyol method was used to obtain ultrasmall ZnO nanoparticles (NPs) doped with iron ions and coated with a low molecular weight fucoidan in order to perform in vivo MR and ex vivo fluorescence imaging of athrothrombosis. During the synthesis, the early elimination of water by azeotropic distillation with toluene allowed us to produce NPs which size, determined by XRD and TEM, decreased from 7 nm to 4 nm with the increase of iron/zinc ratios from 0.05 to 0.50 respectively. For the highest iron content (NP-0.50) NPs were evidenced as a mixture of nanocrystals made of wurtzite and cubic phase with a molar ratio of 2.57:1, although it was not possible to distinguish one from the other by TEM. NP-0.50 were superparamagnetic and exhibited a large emission spectrum at 470 nm when excited at 370 nm. After surface functionalization of NP-0.50 with fucoidan (fuco-0.50), the hydrodynamic size in the physiological medium was 162.0 ± 0.4 nm, with a corresponding negative zeta potential of −48.7 ± 0.4 mV, respectively. The coating was evidenced by FT-IR spectra and thermogravimetric analysis. Aqueous suspensions of fuco-0.50 revealed high transverse proton relaxivities (T2) with an r2 value of 173.5 mM−1 s−1 (300 K, 7.0 T) and remained stable for more than 3 months in water or in phosphate buffer saline without evolution of the hydrodynamic size and size distribution. No cytotoxic effect was observed on human endothelial cells up to 48 h with these NPs at a dose of 0.1 mg/mL. After injection into a rat model of atherothrombosis, MR imaging allowed the localization of diseased areas and the subsequent fluorescence imaging of thrombus on tissue slices. View Full-Text
Keywords: zinc oxide; iron oxide; nanoparticles; fucoidan; atherothrombosis; MRI; optical imaging; contrast agents zinc oxide; iron oxide; nanoparticles; fucoidan; atherothrombosis; MRI; optical imaging; contrast agents
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Nguyen, H.; Tinet, E.; Chauveau, T.; Geinguenaud, F.; Lalatonne, Y.; Michel, A.; Aid-Launais, R.; Journé, C.; Lefèbvre, C.; Simon-Yarza, T.; Motte, L.; Jouini, N.; Tualle, J.-M.; Chaubet, F. Bimodal Fucoidan-Coated Zinc Oxide/Iron Oxide-Based Nanoparticles for the Imaging of Atherothrombosis. Molecules 2019, 24, 962.

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