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.
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.
Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, PA, 19104-60608, USA. muzykant@mail.med.upenn.edu
V R
VR
Muzykantov
M
M
Christofidou-Solomidou
I
I
Balyasnikova
D W
DW
Harshaw
L
L
Schultz
A B
AB
Fisher
S M
SM
Albelda
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D019921:Biotinylation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D000922:Immunotoxins / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D019809:Streptavidin / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution; D014471:Umbilical Veins
D000906:Antibodies; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D005293:Ferritins; D019809:Streptavidin