title: Functionalizing Liposomes with anti-CD44 Aptamer for Selective Targeting of Cancer Cells.
abstract: CD44 receptor protein is found to be overexpressed by many tumors and is identified as one of the most common cancer stem cell surface markers including tumors affecting colon, breast, pancreas, and head and neck, making this an attractive receptor for therapeutic targeting. In this study, 2'-F-pyrimidine-containing RNA aptamer (Apt1), previously selected against CD44, was successfully conjugated to the surface of PEGylated liposomes using the thiol-maleimide click reaction. The conjugation of Apt1 to the surface of liposomes was confirmed by the change in size and zeta potential and by migration on agarose gel electrophoresis. The binding affinity of Apt1 was improved after conjugation compared to free-Apt1. The cellular uptake for Apt1-Lip was tested by flow cytometry and confocal imaging using the two CD44(+) cell lines, human lung cancer cells (A549) and human breast cancer cells (MDA-MB-231), and the CD44(-) cell line, mouse embryonic fibroblast cells (NIH/3T3). The results showed higher sensitivity and selectivity for Apt1-Lip compared to the blank liposomes (Mal-Lip). In conclusion, we demonstrate a successful conjugation of anti-CD44 aptamer to the surface of liposome and binding preference of Apt1-Lip to CD44-expressing cancer cells and conclude to a promising potency of Apt1-Lip as a specific drug delivery system.
authors.affiliation: †Univ Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.|‡CNRS UMR 8612, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.|§Molecular Biology Research Laboratory, Faculty of Medicine, University of Jordan, Amman 11942, Jordan.
authors.forename: Walhan
authors.initials: W
authors.lastname: Alshaer
authors.affiliation: †Univ Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.|‡CNRS UMR 8612, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Hillaireau
authors.affiliation: †Univ Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.|‡CNRS UMR 8612, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Vergnaud
authors.affiliation: §Molecular Biology Research Laboratory, Faculty of Medicine, University of Jordan, Amman 11942, Jordan.
authors.forename: Said
authors.initials: S
authors.lastname: Ismail
authors.affiliation: †Univ Paris-Sud, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.|‡CNRS UMR 8612, Institut Galien Paris-Sud, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D052157:Aptamers, Nucleotide; D018960:Hyaluronan Receptors; D008081:Liposomes