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Acrylic microspheres in vivo. X. Elimination of circulating cells by active targeting using specific monoclonal antibodies bound to microparticles
Authors:T Laakso  J Andersson  P Artursson  P Edman  I Sj?holm
Affiliation:1. Division of Pharmacy, Department of Drugs, National Board of Health and Welfare, Box 607, S-751 25 Uppsala, Sweden;2. Department of Pharmaceutical Biochemistry, Uppsala, Sweden;3. Department of Medical Immunology, Biomedical Center, University of Uppsala, Uppsala, Sweden;1. Institute of Physical Metallurgy and Metal Physics, RWTH Aachen University, D-52056 Aachen, Germany;2. Aachen Institute for Advanced Study in Computational Engineering Science (AICES), RWTH Aachen University, D-52056 Aachen, Germany;1. Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, United Kingdom;2. Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom;1. Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL, USA;2. Department of Biology, Genetics Institute, Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL, USA;3. Thermo Fisher Scientific, West Palm Beach, FL, USA;4. Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA;5. Proteomics and Mass Spectrometry, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL, USA
Abstract:The elimination from the blood of 51Cr-labelled mouse erythrocytes modified with trinitrophenyl (TNP) groups was followed in mice. After 24 hours, when a stable concentration of the labelled erythrocytes has been attained, monoclonal anti-TNP-antibodies were given intravenously, either in free, soluble form, or bound to microparticles containing immobilized protein A. The anti-TNP-antibodies induced a rapid elimination of the TNP- and 51Cr-labelled erythrocytes. Over the 8-hours time period studied, the elimination rate was significantly faster when the antibodies were administered bound to the particles. After the elimination of the target cells, the radioactivity was found in the liver, spleen and bone marrow. These results and relevant control experiments indicate that a solid carrier 1. can be directed to a specific target cell with a specific antibody and 2. can induce a rapid elimination of the target cell from the circulation.
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