Antibody Drags Nanoparticle Into Lung Cells
Cells use several methods to transport molecules through their cell membranes, most of which depend on a specific recognition event between those molecules and receptors on the cell surface. Now, researchers at the Sidney Kimmel Cancer Center have taken advantage of one of these receptors, found only on the surface of blood vessels in the lung, to transport nanoparticles specifically into lung tissue. The investigators have even been able to image this transport process taking place.
Jan Schnitzer, M.D., principal investigator of a National Cancer Institute Platform Partnership, and his collaborators first identified a molecule on lung endothelial cellsthe cells that line blood vesselsthat acts to trigger a process known as caveolae-mediated transport. Caveolae are horseshoe-shaped indentations in the cell membrane that surround transportable molecules once they bind to specific cell-surface molecules. In their stage of this project, the investigators identified a protein called aminopeptidase P (APP) as being one of these triggering molecules. They then developed a monoclonal antibody that binds only to APP and attached that antibody to gold nanoparticles.
Imaging experiments, using several different techniques, showed conclusively that this antibody was able to target lung tissue specifically. When the antibody bound to its target, cells rapidly took up the antibody and the attached nanoparticles. Whole-body imaging experiments showed that only lung tissue took up the antibody-nanoparticle construct. The researchers published their results in the journal Nature Biotechnology.
This work, which was funded in part by the National Cancer Institute's Alliance for Nanotechnology in Cancer, is detailed in the paper "Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung." Investigators at the University of California, Los Angeles, Gamma Medica, Inc., and the University of Alabama at Birmingham also participated in this study. An abstract of this paper is available through PubMed.