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Open AccessArticle

Endothelial Cell Targeting by cRGD-Functionalized Polymeric Nanoparticles under Static and Flow Conditions

1
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands
2
CDL Research, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
3
Hubrecht Imaging Center, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
4
Division of Cell Biology, Neurobiology and Biophysics, Department of Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Nanomaterials 2020, 10(7), 1353; https://doi.org/10.3390/nano10071353
Received: 2 June 2020 / Revised: 30 June 2020 / Accepted: 7 July 2020 / Published: 10 July 2020
(This article belongs to the Special Issue Nanomaterials for Biomedical Applications)
Since αvβ3 integrin is a key component of angiogenesis in health and disease, Arg-Gly-Asp (RGD) peptide-functionalized nanocarriers have been investigated as vehicles for targeted delivery of drugs to the αvβ3 integrin-overexpressing neovasculature of tumors. In this work, PEGylated nanoparticles (NPs) based on poly(lactic-co-glycolic acid) (PLGA) functionalized with cyclic-RGD (cRGD), were evaluated as nanocarriers for the targeting of angiogenic endothelium. For this purpose, NPs (~300 nm) functionalized with cRGD with different surface densities were prepared by maleimide-thiol chemistry and their interactions with human umbilical vein endothelial cells (HUVECs) were evaluated under different conditions using flow cytometry and microscopy. The cell association of cRGD-NPs under static conditions was time-, concentration- and cRGD density-dependent. The interactions between HUVECs and cRGD-NPs dispersed in cell culture medium under flow conditions were also time- and cRGD density-dependent. When washed red blood cells (RBCs) were added to the medium, a 3 to 8-fold increase in NPs association to HUVECs was observed. Moreover, experiments conducted under flow in the presence of RBC at physiologic hematocrit and shear rate, are a step forward in the prediction of in vivo cell–particle association. This approach has the potential to assist development and high-throughput screening of new endothelium-targeted nanocarriers. View Full-Text
Keywords: nanoparticles; endothelial cells; RGD; targeting; physiological flow; PLGA nanoparticles; endothelial cells; RGD; targeting; physiological flow; PLGA
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Martínez-Jothar, L.; Barendrecht, A.D.; de Graaff, A.M.; Oliveira, S.; van Nostrum, C.F.; Schiffelers, R.M.; Hennink, W.E.; Fens, M.H.A.M. Endothelial Cell Targeting by cRGD-Functionalized Polymeric Nanoparticles under Static and Flow Conditions. Nanomaterials 2020, 10, 1353.

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