Leukocyte mimetic polysaccharide microparticles tracked in vivo on activated endothelium and in abdominal aortic aneurysm.
We have developed injectable microparticles functionalized with fucoidan, in which sulfated groups mimic the anchor sites of P-selectin glycoprotein ligand-1 (PSGL-1), one of the principal receptors supporting leukocyte adhesion. These targeted microparticles were combined with a fluorescent dye and a T2(∗) magnetic resonance imaging (MRI) contrast agent, and then tracked in vivo with small animal imaging methods. Microparticles of 2.5μm were obtained by a water-in-oil emulsification combined with a cross-linking process of polysaccharide dextran, fluorescein isothiocyanate dextran, pullulan and fucoidan mixed with ultrasmall superparamagnetic particles of iron oxide. Fluorescent intravital microscopy observation revealed dynamic adsorption and a leukocyte-like behaviour of fucoidan-functionalized microparticles on a calcium ionophore induced an activated endothelial layer of a mouse mesentery vessel. We observed 20times more adherent microparticles on the activated endothelium area after the injection of functionalized microparticles compared to non-functionalized microparticles (197±11 vs. 10±2). This imaging tool was then applied to rats presenting an elastase perfusion model of abdominal aortic aneurysm (AAA) and 7.4T in vivo MRI was performed. Visual analysis of T2(∗)-weighted MR images showed a significant contrast enhancement on the inner wall of the aneurysm from 30min to 2h after the injection. Histological analysis of AAA cryosections revealed microparticles localized inside the aneurysm wall, in the same areas in which immunostaining shows P-selectin expression. The developed leukocyte mimetic imaging tool could therefore be relevant for molecular imaging of vascular diseases and for monitoring biologically active areas prone to rupture in AAA.
Inserm, U1148, Laboratory for Vascular Translational Science (LVTS), X. Bichat Hospital, 46 rue H. Huchard, F-75018 Paris, France; Institut Galilée, Université Paris 13, Sorbonne Paris Cité, F-93430 Villetaneuse, France.
Thomas
T
Bonnard
IFR 02, UFR de Médecine, site Bichat, Université Paris Diderot, F-75018 Paris, France.
Jean-Michel
JM
Serfaty
IFR 02, UFR de Médecine, site Bichat, Université Paris Diderot, F-75018 Paris, France.
Clément
C
Journé
Inserm, U1148, Laboratory for Vascular Translational Science (LVTS), X. Bichat Hospital, 46 rue H. Huchard, F-75018 Paris, France.
Benoît
B
Ho Tin Noe
Inserm, U1148, Laboratory for Vascular Translational Science (LVTS), X. Bichat Hospital, 46 rue H. Huchard, F-75018 Paris, France.
Denis
D
Arnaud
Inserm, U1148, Laboratory for Vascular Translational Science (LVTS), X. Bichat Hospital, 46 rue H. Huchard, F-75018 Paris, France.
Liliane
L
Louedec
Inserm, U1148, Laboratory for Vascular Translational Science (LVTS), X. Bichat Hospital, 46 rue H. Huchard, F-75018 Paris, France.
Sidi Mohammed
SM
Derkaoui
Inserm, U1148, Laboratory for Vascular Translational Science (LVTS), X. Bichat Hospital, 46 rue H. Huchard, F-75018 Paris, France; Institut Galilée, Université Paris 13, Sorbonne Paris Cité, F-93430 Villetaneuse, France.
Didier
D
Letourneur
Inserm, U1148, Laboratory for Vascular Translational Science (LVTS), X. Bichat Hospital, 46 rue H. Huchard, F-75018 Paris, France; Institut Galilée, Université Paris 13, Sorbonne Paris Cité, F-93430 Villetaneuse, France.
Cédric
C
Chauvierre
Inserm, U1148, Laboratory for Vascular Translational Science (LVTS), X. Bichat Hospital, 46 rue H. Huchard, F-75018 Paris, France; Institut Galilée, Université Paris 13, Sorbonne Paris Cité, F-93430 Villetaneuse, France. Electronic address: catherine.levisage@inserm.fr.
Catherine
C
Le Visage
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology; D040761:Biomimetic Materials / Q000737:chemistry / Q000493:pharmacokinetics; D055252:Cell-Derived Microparticles / Q000737:chemistry / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods; D011134:Polysaccharides / Q000493:pharmacokinetics*
D011134:Polysaccharides; C007789:fucoidan
Fucoidan; Intravital microscopy; MRI; P-selectin