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Shear‐regulated uptake of nanoparticles by endothelial cells and development of endothelial‐targeting nanoparticles
Author(s) -
Lin Arthur,
Sabnis Abhimanyu,
Kona Soujanya,
Nattama Sivaniaravindapriya,
Patel Hemang,
Dong JingFei,
Nguyen Kytai T.
Publication year - 2009
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32592
Subject(s) - biophysics , adhesion , materials science , nanoparticle , cell adhesion , fluorescence microscope , endothelial stem cell , confocal microscopy , extracellular , nanotechnology , microbiology and biotechnology , in vitro , chemistry , fluorescence , biochemistry , biology , physics , quantum mechanics , composite material
Abstract The purpose of this research project was to develop nanoparticles with improved targeting, adhesion, and cellular uptake to activated or inflamed endothelial cells (ECs) under physiological flow conditions. Our hypothesis is that by mimicking platelet binding to activated ECs through the interaction between platelet glycoprotein Ibα (GP Ibα) and P‐selectin on activated endothelial cells, GP Ibα‐conjugated nanoparticles could exhibit increased targeting and higher cellular uptake in injured or activated endothelial cells under physiological flow conditions. To test this hypothesis, fluorescent‐carboxylated polystyrene nanoparticles were selected for the study as a model particle because of its narrow size distribution as a “proof‐of‐concept.” Using confocal microscopy, fluorescent measurements, and protein assays, cellular uptake properties were characterized for these polystyrene nanoparticles. The study also found that conjugation of 100‐nm polystyrene nanoparticles with glycocalicin (the extracellular segment of GP Ibα) significantly increased the particle adhesion on P‐selectin‐coated surfaces and cellular uptake of nanoparticles by activated endothelial cells under physiological flow conditions. The results demonstrate that these novel endothelial‐targeting nanoparticles could be the first step toward developing a targeted and sustained drug delivery system that can improve shear‐regulated particle adhesion and cellular uptake. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010