Streptavidin facilitates internalization and pulmonary targeting of an anti-endothelial cell antibody (platelet-endothelial cell adhesion molecule 1): A strategy for vascular immunotargeting of drugs
| Autor: | David W. Harshaw, Steven M. Albelda, Aron B. Fisher, Irina V. Balyasnikova, Melpo Christofidou-Solomidou, Vladimir R. Muzykantov, Linda B. Schultz |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Streptavidin Umbilical Veins Endothelium media_common.quotation_subject Antibodies Iodine Radioisotopes Rats Sprague-Dawley Mice chemistry.chemical_compound Antigen Immunotoxin medicine Animals Humans Biotinylation Tissue Distribution Internalization Lung Cells Cultured media_common Multidisciplinary biology Immunotoxins Biological Transport Biological Sciences Molecular biology Rats Platelet Endothelial Cell Adhesion Molecule-1 Kinetics medicine.anatomical_structure Targeted drug delivery chemistry Ferritins embryonic structures cardiovascular system biology.protein Endothelium Vascular Rabbits Antibody tissues |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:2379-2384 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Conjugation of drugs with antibodies to surface endothelial antigens is a potential strategy for drug delivery to endothelium. We studied antibodies to platelet-endothelial adhesion molecule 1 (PECAM-1, a stably expressed endothelial antigen) as carriers for vascular immunotargeting. Although 125 I-labeled anti-PECAM bound to endothelial cells in culture, the antibody was poorly internalized by the cells and accumulated poorly after intravenous administration in mice and rats. However, conjugation of biotinylated anti-PECAM (b-anti-PECAM) with streptavidin (SA) markedly stimulated uptake and internalization of anti-PECAM by endothelial cells and by cells expressing PECAM. In addition, conjugation with streptavidin markedly stimulated uptake of 125 I-labeled b-anti-PECAM in perfused rat lungs and in the lungs of intact animals after either intravenous or intraarterial injection. The antioxidant enzyme catalase conjugated with b-anti-PECAM/SA bound to endothelial cells in culture, entered the cells, escaped intracellular degradation, and protected the cells against H 2 O 2 -induced injury. Anti-PECAM/SA/ 125 I-catalase accumulated in the lungs after intravenous injection or in the perfused rat lungs and protected these lungs against H 2 O 2 -induced injury. Thus, modification of a poor carrier antibody with biotin and SA provides an approach for facilitation of antibody-mediated drug targeting. Anti-PECAM/SA is a promising candidate for vascular immunotargeting of bioactive drugs. |
| Databáze: | OpenAIRE |
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