title: Development of a platform of antibody-presenting liposomes.
abstract: Antibody-presenting liposomes present high interest as drug delivery systems. The association of antibodies to liposomes is usually realized by covalent coupling of IgGs or their antigen-binding fragments to lipid polar head groups by means of hetero-bifunctional crosslinkers. We present here an original platform of IgG-presenting liposomes which is based on a fusion protein between Annexin-A5 (Anx5) and the IgG-binding ZZ repeat derived from Staphylococcus aureus protein A. The Anx5ZZ fusion protein acts as a bi-functional adaptor that anchors IgGs to liposomes in a non covalent and highly versatile manner. The interactions between IgGs, Anx5ZZ and liposomes were characterized by PAGE, dynamic light scattering and fluorescence quenching assays, establishing that binding of Anx5ZZ to IgGs and of Anx5ZZ-IgG complexes to liposomes is complete with stoichiometric amounts of each species. We found that the sequence of assembly is important and that Anx5ZZ-IgG complexes need to be formed first in solution and then adsorbed to liposomes in order to avoid aggregation. The targeting capacity of Anx5ZZ-IgG-functionalized liposomes was demonstrated by electron microscopy on an ex vivo model system of atherosclerotic plaques. This study shows that the Anx5ZZ adaptor constitutes an efficient platform for functionalizing liposomes with IgGs. This platform may present potential applications in molecular imaging and drug delivery.
authors.affiliation: Molecular Imaging and NanoBioTechnology, IECB, UMR-5248 CBMN, CNRS-University Bordeaux1-ENITAB, Avenue des Facultés, 33402, Talence, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Garnier
authors.forename: Sisareuth
authors.initials: S
authors.lastname: Tan
authors.forename: Céline
authors.initials: C
authors.lastname: Gounou
authors.forename: Alain R
authors.initials: AR
authors.lastname: Brisson
authors.forename: Jeanny
authors.initials: J
authors.lastname: Laroche-Traineau
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Jacobin-Valat
authors.forename: Gisèle
authors.initials: G
authors.lastname: Clofent-Sanchez
mesh_terms: D017304:Annexin A5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013205:Staphylococcal Protein A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D007074:Immunoglobulin G; D008081:Liposomes; D011994:Recombinant Proteins; D013205:Staphylococcal Protein A