Gd(DOTA)-grafted submicronic polysaccharide-based particles functionalized with fucoidan as potential MR contrast agent able to target human activated platelets

• Published in: Carbohydrate polymers Vol. 245; p. 116457
• Main Authors: Forero Ramirez, Laura Marcela, Gobin, Elise, Aid-Launais, Rachida, Journe, Clément, Moraes, Fernanda C., Picton, Luc, Le Cerf, Didier, Letourneur, Didier, Chauvierre, Cédric, Chaubet, Frédéric
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2020; Elsevier
• Subjects: Adult; Blood Platelets - chemistry; Cells, Cultured; Contrast Media - chemistry; Cross-Linking Reagents - chemistry; crosslinking; Dextran; Dextrans - chemistry; Emulsions - chemistry; fucoidan; Gadolinium - chemistry; Healthy Volunteers; Heterocyclic Compounds - chemistry; Heterocyclic Compounds, 1-Ring - chemistry; human platelets; Human Umbilical Vein Endothelial Cells; Humans; Life Sciences; Macromolecular Substances - chemistry; Magnetic Resonance Imaging - methods; MRI; Nanoparticles - chemistry; Organometallic Compounds - chemistry; Particle Size; Platelet Activation; Polysaccharides - chemistry; Spectrometry, X-Ray Emission - methods; submicronic particles; Thrombosis - diagnosis; Dextran; submicronic particles; MRI; fucoidan; crosslinking; human platelets
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2020.116457

[Display omitted] •Polysaccharide matrix contained both fucoidan and dextran gadolinium macrocomplex.•A simple and green water-in-oil emulsification/crosslinking method was developed.•Particles are cytocompatible with human endothelial cells.•Particles successfully targeted activated human platelets via fucoidan/P-selectin interactions.•Dual T1/T2 relaxation properties were confirmed on MRI phantoms. Early detection of thrombotic events remains a big medical challenge. Dextran-based submicronic particles bearing Gd(DOTA) groups and functionalized with fucoidan have been produced via a simple and green water-in-oil emulsification/co-crosslinking process. Their capacity to bind to human activated platelets was evidenced in vitro as well as their cytocompatibility with human endothelial cells. The presence of Gd(DOTA) moieties was confirmed by elemental analysis and total reflection X-ray fluorescence (TRXF) spectrometry. Detailed characterization of particles was performed in terms of size distribution, morphology, and relaxation rates. In particular, longitudinal and transversal proton relaxivities were respectively 1.7 and 5.0 times higher than those of DOTAREM. This study highlights their potential as an MRI diagnostic platform for atherothrombosis.