Preparation of E-selectin-targeting nanoparticles and preliminary in vitro evaluation.
Targeted delivery aims to concentrate therapeutic agents at their site of action and thereby enhance treatment and limit side-effects. E-selectin on endothelial cells is markedly up-regulated by cytokine stimulation of inflamed and some tumoral tissues, promoting the adhesion of leukocytes and metastatic tumor cells, thus making it an interesting molecular target for drug delivery systems. We report here the preparation of targeted nanoparticles from original amphiphilic block copolymers functionalized with an analog of sialyl Lewis X (SLEx), the physiological ligand of E-selectin. Nanoparticles, prepared by nanoprecipitation, caused no significant cytotoxicity. Ligand-functionalized nanoparticles were specifically recognized and internalized better by tumor necrosis factor α (TNF-α)-activated human umbilical vein endothelial cells (HUVECs) than control nanoparticles or HUVECs with low E-selectin expression. These nanoparticles are designed to carry the ligand at the end of a PEG spacer to improve accessibility. This system has potential for the treatment of inflammation, inhibition of tumor metastasis, and for molecular imaging.
Université Paris-Sud11, Faculté de Pharmacie, 5 rue J.B. Clément CHATENAY-MALABRY, FR 92296, UMR 8612 CNRS, LabEx LERMIT, France.
Emile
E
Jubeli
Université Paris-Sud11, Faculté de Pharmacie, 5 rue J.B. Clément CHATENAY-MALABRY, FR 92296, UMR 8612 CNRS, LabEx LERMIT, France.
Laurence
L
Moine
Université Paris-Sud11, Faculté de Pharmacie, 5 rue J.B. Clément CHATENAY-MALABRY, FR 92296, Plateforme d'Imagerie Cellulaire, LabEx LERMIT, France.
Valérie
V
Nicolas
Université Paris-Sud11, Faculté de Pharmacie, 5 rue J.B. Clément CHATENAY-MALABRY, FR 92296, UMR 8612 CNRS, LabEx LERMIT, France. Electronic address: gillian.barratt@u-psud.fr.
Gillian
G
Barratt
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D019040:E-Selectin / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D016256:Lewis X Antigen / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008689:Methacrylates / Q000138:chemical synthesis; D018613:Microscopy, Confocal; D053758:Nanoparticles; D036103:Nanotechnology; D011091:Polyesters / Q000138:chemical synthesis; D011092:Polyethylene Glycols / Q000138:chemical synthesis; D011108:Polymers / Q000138:chemical synthesis* / Q000633:toxicity; D000080506:Sialyl Lewis X Antigen; D013050:Spectrometry, Fluorescence; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004337:Drug Carriers; D019040:E-Selectin; D016256:Lewis X Antigen; D008024:Ligands; D008689:Methacrylates; D011091:Polyesters; D011108:Polymers; C546936:SELE protein, human; D000080506:Sialyl Lewis X Antigen; D014409:Tumor Necrosis Factor-alpha; C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols; C033616:poly(lactide)