Cellular uptake of liposomes targeted to intercellular adhesion molecule-1 (ICAM-1) on bronchial epithelial cells

Abstract

Previously, it was demonstrated that immunoliposomes, bearing anti-intercellular adhesion molecule-1 (ICAM-1) antibodies (mAb F10.2), can specifically bind to different cell types expressing ICAM-1. In this study, we have quantified the amount of immunoliposomes binding to IFN-gamma activated human bronchial epithelial cells (BEAS-2B) in vitro and studied the subsequent fate of cell-bound anti-ICAM-1 immunoliposomes. We demonstrate that binding of the immunoliposomes to the epithelial cells depends on the liposome concentration used. After binding to the cell surface, the anti-ICAM-1 immunoliposomes are rapidly internalised by the epithelial cells. Sixty percent of cell-bound immunoliposomes were internalised by the epithelial cells within 1 h of incubation at 37 degrees C. The results indicate that ICAM-1 targeted immunoliposomes may be used as carriers for the intracellular delivery of anti-inflammatory drugs to sites of inflammation characterised by an increased expression of ICAM-1.

ICAM-directed vascular immunotargeting of antithrombotic agents to the endothelial luminal surface

“…Published studies on anti-ICAM internalization have yielded inconsistent results: epithelial and blood cells have been reported to internalize ICAM ligands in vitro, 45,46 but fragmentary data in other cell types showed the opposite outcome. 47,48 Our studies in cell culture, perfused rat lungs, and in animals show that endothelial cells internalize ICAM antibodies poorly (Figures 1, 2, 3, and 6).…”

Immunoliposomes Directed Toward VCAM-1 Interact Specifically with Activated Endothelial Cells—A Potential Tool for Specific Drug Delivery

“…To record the kinetic of internalization, HEC were incubated with 3 H-cholesterol labeled plain liposomes, specific and unspecific immunoliposomes at a concentration of 1 mmol liposomes/10 6 cells, for 1, 2, 4, and 24 h at 37-C. At indicated time target intervals, the cells were washed three times with cold PBS-C and incubated (5 min) with 40 mM citric acid, 120 mM NaCl, pH 3, a treatment that has been shown to remove all liposomes bound to the cell surface without disrupting the cell membrane (5,20). Then the cells were solubilized in 0.2 N NaOH (overnight at 4-C), and radioactivity was measured with a liquid scintillation counter (Beckman Counter LS 100C).…”

ICAM-1 recycling in endothelial cells: a novel pathway for sustained intracellular delivery and prolonged effects of drugs

“…[4][5][6][7] Antibodies to ICAM-1 are being explored as therapeutics and affinity carriers in cell cultures, animal models, and early clinical studies. [8][9][10][11][12][13] In addition to acting as delivery vehicles, antibody blocking of ICAM-1 suppresses leukocyte adhesion to ECs, providing an anti-inflammatory benefit to the effects of drugs. 14,15 Targeting nanocarriers (NCs) to EC determinants decreases the clearance of drugs from the bloodstream and permits site-specific delivery, increasing therapeutic capacity and reducing side effects (Muzykantov 16 ).…”