Premium
Cell‐selective intracellular delivery of a foreign enzyme to endothelium in vivo using vascular immunotargeting
Author(s) -
SCHERPEREEL ARNAUD,
WIEWRODT RAINER,
CHRISTOFIDOUSOLOMIDOU MELPO,
GERVAIS RADJ,
MURCIANO JUANCARLOS,
ALBELDA STEVEN M.,
MUZYKANTOV VLADIMIR R.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0022com
Subject(s) - endothelium , internalization , intracellular , antibody , antigen , spleen , endothelial stem cell , microbiology and biotechnology , biology , in vivo , chemistry , cell , immunology , in vitro , biochemistry , endocrinology
Vascular immunotargeting, the administration of drugs conjugated with antibodies to endothelial surface antigens, has the potential for drug delivery to the endothelium. Our previous cell culture studies showed that biotinylated antibodies to PECAM‐1 (a highly expressed endothelial surface antigen) coupled with streptavidin (SA, a cross‐linking protein that facilitates anti‐PECAM internalization and targeting) may provide a carrier for the intracellular delivery of therapeutic enzymes. This paper describes the PECAM‐directed vascular immunotargeting of a reporter enzyme (β‐galactosidase, β‐Gal) in intact animals. Intravenous injection of [ 125 I]SA‐β‐Gal conjugated with either anti‐PECAM or IgG led to a high 125 I uptake in liver and spleen, yet β‐Gal activity in these organs rapidly declined to the background levels, suggesting rapid degradation of the conjugates. In contrast, anti‐PECAM/[ 125 I]SA‐β‐Gal, but not IgG/[ 125 I]SA‐β‐Gal, accumulated in the lungs (36.0±1.3 vs. 3.9±0.6% injected dose/g) and induced a marked elevation of β‐Gal activity in the lung tissue persisting for up to 8 h after injection (10‐fold elevation 4 h postinjection). Using histochemical detection, the β‐Gal activity in the lungs was detected in the endothelial cells of capillaries and large vessels. The anti‐PECAM carrier also provided 125 I uptake and β‐Gal activity in the renal glomeruli. Predominant intracellular localization of anti‐PECAM/SA‐β‐Gal was documented in the PECAM‐expressing cells in culture by confocal microscopy and in the pulmonary endothelium by electron microscopy. Therefore, vascular immunotargeting is a feasible strategy for cell‐selective, intracellular delivery of an active foreign enzyme to endothelial cells in vivo , and thus may be potentially useful for the treatment of acute pulmonary or vascular diseases.—Scherpereel, A., Wiewrodt, R., Christofidou‐Solomidou, M., Gervais, R., Murciano, J.‐C., Albelda, S. M., Muzykantov, V. R. Cell‐selective intracellular delivery of a foreign enzyme to endothelium in vivo using vascular immunotargeting. FASEB J. 15, 416‐426 (2001).