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Nanomaterials 2018, 8(6), 358; https://doi.org/10.3390/nano8060358

Interaction of Poly(l-lysine)/Polysaccharide Complex Nanoparticles with Human Vascular Endothelial Cells

1
Deutsches Krebsforschungszentrum (DKFZ), Clinical Cooperation Unit Applied Tumor Immunology, D-69120 Heidelberg, Germany
2
Institute of Plant and Wood Chemistry, Technische Universität Dresden, D-01737 Tharandt, Germany
3
Deutsches Krebsforschungszentrum (DKFZ), Central Unit Electron Microscopy, D-69120 Heidelberg, Germany
4
Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
5
Department Polyelectrolytes and Dispersions, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, D-01069 Dresden, Germany
6
Department of Chemistry and Food Chemistry, Technische Universität Dresden, D-01062 Dresden, Germany
*
Author to whom correspondence should be addressed.
Received: 17 April 2018 / Revised: 7 May 2018 / Accepted: 15 May 2018 / Published: 23 May 2018
(This article belongs to the Special Issue Nanocolloids for Nanomedicine and Drug Delivery)
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Abstract

Angiogenesis plays an important role in both soft and hard tissue regeneration, which can be modulated by therapeutic drugs. If nanoparticles (NP) are used as vectors for drug delivery, they have to encounter endothelial cells (EC) lining the vascular lumen, if applied intravenously. Herein the interaction of unloaded polyelectrolyte complex nanoparticles (PECNP) composed of cationic poly(l-lysine) (PLL) and various anionic polysaccharides with human vascular endothelial cells (HUVEC) was analyzed. In particular PECNP were tested for their cell adhesive properties, their cellular uptake and intracellular localization considering composition and net charge. PECNP may form a platform for both cell coating and drug delivery. PECNP, composed of PLL in combination with the polysaccharides dextran sulfate (DS), cellulose sulfate (CS) or heparin (HEP), either unlabeled or labeled with fluorescein isothiocyanate (FITC) and either with positive or negative net charge were prepared. PECNP were applied to human umbilical cord vein endothelial cells (HUVEC) in both, the volume phase and immobilized phase at model substrates like tissue culture dishes. The attachment of PECNP to the cell surface, their intracellular uptake, and effects on cell proliferation and growth behavior were determined. Immobilized PECNP reduced attachment of HUVEC, most prominently the systems PLL/HEP and PLL/DS. A small percentage of immobilized PECNP was taken up by cells during adhesion. PECNP in the volume phase showed no effect of the net charge sign and only minor effects of the composition on the binding and uptake of PECNP at HUVEC. PECNP were stored in endosomal vesicles in a cumulative manner without apparent further processing. During mitosis, internalized PECNP were almost equally distributed among the dividing cells. Both, in the volume phase and immobilized at the surface, PECNP composed of PLL/HEP and PLL/DS clearly reduced cell proliferation of HUVEC, however without an apparent cytotoxic effect, while PLL/CS composition showed minor impairment. PECNP have an anti-adhesive effect on HUVEC and are taken up by endothelial cells which may negatively influence the proliferation rate of HUVEC. The negative effects were less obvious with the composition PLL/CS. Since uptake and binding for PLL/HEP was more efficient than for PLL/DS, PECNP of PLL/HEP may be used to deliver growth factors to endothelial cells during vascularization of bone reconstitution material, whereas those of PLL/CS may have an advantage for substituting biomimetic bone scaffold material. View Full-Text
Keywords: poly(l-lysine); cellulose sulfate; dextran sulfate; heparin; polyelectrolyte complex nanoparticle (PECNP); vascular endothelial cells; cell attachment; cellular uptake; proliferation poly(l-lysine); cellulose sulfate; dextran sulfate; heparin; polyelectrolyte complex nanoparticle (PECNP); vascular endothelial cells; cell attachment; cellular uptake; proliferation
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Weber, D.; Torger, B.; Richter, K.; Nessling, M.; Momburg, F.; Woltmann, B.; Müller, M.; Schwartz-Albiez, R. Interaction of Poly(l-lysine)/Polysaccharide Complex Nanoparticles with Human Vascular Endothelial Cells. Nanomaterials 2018, 8, 358.

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