title: Adhesion of antibody-functionalized polymersomes.
abstract: Polymersomes are vesicles made from synthetic block copolymers. The adhesiveness of micron-sized polymersomes, functionalized with antibodies that bind to vascular cell adhesion molecules, which could be useful for vascular targeting, was measured. Intercellular adhesion molecule-1 (ICAM-1) is an endothelial cell adhesion molecule whose expression increases during inflammatory disease, and is therefore a natural target for vascular delivery. We functionalized polymersomes with an anti-ICAM-1 antibody, using modular biotin-avidin chemistry. Micropipet aspiration was used to confirm specific adhesion and measure the adhesion strength between an anti-ICAM-1-coated polymersome and an ICAM-1-coated polystyrene microsphere at various surface densities of adhesion molecules. The adhesion is kinetically trapped, and adhesion strength is quantified by the critical tension for detachment. The adhesion strength increases in proportion to the surface density of anti-ICAM-1 molecules, in contrast to results seen previously when measuring adhesion between biotinylated vesicles and avidin-coated beads (Lin et al. Langmuir 2004, 20, 5493). The difference in dependence on the density of functional groups is likely due to the molecular presentation at the vesicle surface; in the current study, the presentation of biotinylated anti-ICAM-1 on a layer of avidin leads to the effective presentation of the anti-ICAM-1 and, thus, a monotonic increase in adhesiveness with antibody density.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Lin
authors.forename: P Peter
authors.initials: PP
authors.lastname: Ghoroghchian
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hammer
mesh_terms: D000268:Adhesiveness; D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D001360:Avidin / Q000737:chemistry; D001704:Biopolymers / Q000737:chemistry*; D001710:Biotin / Q000737:chemistry; D005456:Fluorescent Dyes; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000276:immunology; D008863:Microspheres; D046912:Multiprotein Complexes / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D013499:Surface Properties
chemical_list: D000906:Antibodies; D001704:Biopolymers; D005456:Fluorescent Dyes; D046912:Multiprotein Complexes; D011137:Polystyrenes; D018799:Intercellular Adhesion Molecule-1; D001360:Avidin; D001710:Biotin