Shear-regulated uptake of nanoparticles by endothelial cells and development of endothelial-targeting nanoparticles.
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 Ibalpha (GP Ibalpha) and P-selectin on activated endothelial cells, GP Ibalpha-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 Ibalpha) 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.
Lin
Arthur
A
Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, USA. knguyen@uta.edu
Sabnis
Abhimanyu
A
Kona
Soujanya
S
Nattama
Sivaniaravindapriya
S
Patel
Hemang
H
Dong
Jing-Fei
JF
Nguyen
Kytai T
KT
D000268:Adhesiveness / Q000187:drug effects; D040761:Biomimetic Materials / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D019007:P-Selectin / Q000378:metabolism; D010316:Particle Size; D019038:Platelet Glycoprotein GPIb-IX Complex; D013314:Stress, Mechanical; D013499:Surface Properties / Q000187:drug effects
D008562:Membrane Glycoproteins; D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor