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

Vladimir R. Muzykantov*, Melpo Christofidou-Solomidou, Irina Balyasnikova, David W. Harshaw, Linda Schultz, Aron B. Fisher, Steven M. Albelda

*Corresponding author for this work

Research output: Contribution to journalArticle

123 Scopus citations

Abstract

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 125I-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 125I-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 H2O2- induced injury. Anti-PECAM/SA/125I, catalase accumulated in the lungs after intravenous injection or in the perfused rat lungs and protected these lungs against H2O2-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.

Original languageEnglish (US)
Pages (from-to)2379-2384
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number5
DOIs
StatePublished - Mar 2 1999

Keywords

  • Bioconjugation
  • Catalase
  • Lung
  • PECAM-1

ASJC Scopus subject areas

  • General

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