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.

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“…Using a modular biotin-avidin chemistry, Lin and colleagues functionalized polymer vesicles with anti-ICAM-1 antibody to target ICAM-1 (intercellular adhesion molecule-1) [21], a molecule that is upregulated on endothelial cells during inflammation. Using micropipette aspiration, they measured the adhesiveness of these functionalized polymer vesicles to ICAM-1 immobilized on the surface of polystyrene beads and determined that the adhesion strength is linearly proportional to the surface density of the anti-ICAM-1 molecules on the polymersome [21].…”

“…Using micropipette aspiration, they measured the adhesiveness of these functionalized polymer vesicles to ICAM-1 immobilized on the surface of polystyrene beads and determined that the adhesion strength is linearly proportional to the surface density of the anti-ICAM-1 molecules on the polymersome [21]. This finding is in contrast to their earlier adhesion experiments carried out with functionalized biotinylated polymersomes and avidin coated beads [22], suggesting that the adhesiveness of functionalized vesicles is not only dependent on surface density, but also upon the presentation/orientation of the targeting molecules on the vesicle surface [21].…”

“…In addition to ICAM-1 molecules, selectins are also upregulated at sites of inflammation [21]. In an effort to create "leukopolymersomes," i.e.…”

“…These investigators were able to measure firm and rolling adhesion of anti-ICAM-1-, sLe x -, and anti-ICAM-1/sLe x conjugated polymersomes under flow along ICAM-1, P-selectin, and ICAM-1/P-selectin coated surfaces, respectively, at venous shear rates. It is believed that dual functionalized leukopolymersomes will be able to serve as targeting agents to bring both therapeutics (drugs) and diagnostics (imaging agents) to sites of inflammation [21].…”

“…In addition, biologically active ligands, such as antibodies, can be readily conjugated to the exterior brush surface to target the vesicles or to provide a therapeutic response [19][20][21][22]. These properties of the vesicle architecture effectively create a multimodal platform, which can be used for therapeutic (drug delivery) and/or diagnostic (imaging) applications (Fig.…”