title: Development of Polymer Microcapsules Functionalized with Fucoidan to Target P-Selectin Overexpressed in Cardiovascular Diseases.
abstract: New tools for molecular imaging and targeted therapy for cardiovascular diseases are still required. Herein, biodegradable microcapsules (MCs) made of polycyanoacrylate and polysaccharide and functionalized with fucoidan (Fuco-MCs) are designed as new carriers to target arterial thrombi overexpressing P-selectin. Physicochemical characterizations demonstrated that microcapsules have a core-shell structure and that fucoidan is present onto the surface of Fuco-MCs. Furthermore, their sizes range from 2 to 6 µm and they are stable on storage over 30 d at 4 °C. Flow cytometry experiments evidenced the binding of Fuco-MCs for human activated platelets as compared to MCs (mean fluorescence intensity: 12 008 vs. 9, p < 0.001) and its absence for nonactivated platelets (432). An in vitro flow adhesion assay showed high specific binding efficiency of Fuco-MCs to P-selectin and to activated platelet aggregates under arterial shear stress conditions. Moreover, both types of microcapsules reveal excellent compatibility with 3T3 cells in cytotoxicity assay. One hour after intravenous injection of microcapsules, histological analysis revealed that Fuco-MCs are localized in the rat abdominal aortic aneurysm thrombotic wall and that the binding in the healthy aorta is low. In conclusion, these microcapsules appear as promising carriers for targeting of tissues characterized by P-selectin overexpression and for their molecular imaging or treatment.
authors.affiliation: INSERM, U1148, Laboratory for Vascular Translational Science, CHU X. Bichat, Paris Diderot University, 46 rue H. Huchard, 75018, Paris, France.|Institut Galilée, Paris 13 University, 99 av JB Clément, 93430, Villetaneuse, France.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: INSERM, U1148, Laboratory for Vascular Translational Science, CHU X. Bichat, Paris Diderot University, 46 rue H. Huchard, 75018, Paris, France.|Institut Galilée, Paris 13 University, 99 av JB Clément, 93430, Villetaneuse, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Juenet
authors.affiliation: INSERM, U1148, Laboratory for Vascular Translational Science, CHU X. Bichat, Paris Diderot University, 46 rue H. Huchard, 75018, Paris, France.|Institut Galilée, Paris 13 University, 99 av JB Clément, 93430, Villetaneuse, France.
authors.forename: Rachida
authors.initials: R
authors.lastname: Aid-Launais
authors.affiliation: INSERM, U1148, Laboratory for Vascular Translational Science, CHU X. Bichat, Paris Diderot University, 46 rue H. Huchard, 75018, Paris, France.|Institut Galilée, Paris 13 University, 99 av JB Clément, 93430, Villetaneuse, France.
authors.forename: Murielle
authors.initials: M
authors.lastname: Maire
authors.affiliation: INSERM, U1148, Laboratory for Vascular Translational Science, CHU X. Bichat, Paris Diderot University, 46 rue H. Huchard, 75018, Paris, France.|Institut Galilée, Paris 13 University, 99 av JB Clément, 93430, Villetaneuse, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Ollivier
authors.affiliation: INSERM, U1148, Laboratory for Vascular Translational Science, CHU X. Bichat, Paris Diderot University, 46 rue H. Huchard, 75018, Paris, France.|Institut Galilée, Paris 13 University, 99 av JB Clément, 93430, Villetaneuse, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Letourneur
authors.affiliation: INSERM, U1148, Laboratory for Vascular Translational Science, CHU X. Bichat, Paris Diderot University, 46 rue H. Huchard, 75018, Paris, France.|Institut Galilée, Paris 13 University, 99 av JB Clément, 93430, Villetaneuse, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Chauvierre
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000378:metabolism; D002214:Capsules; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D019007:P-Selectin / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D002214:Capsules; D019007:P-Selectin; D011134:Polysaccharides; C007789:fucoidan
keywords: P-selectin; fucoidan; molecular targeting; polymer microcapsules; thrombosis