Comparative analysis of nanosystems’ effects on human endothelial and monocytic cell functions

Abstract

The objective of our work was to investigate the effects of different types of nanoparticles on endothelial (HUVEC) and monocytic cell functions. We prepared and tested 14 different nanosystems comprising liposomes, lipid nanoparticles, polymer, and iron oxide nanoparticles. Some of the tested nanosystems contained targeting, therapeutic, or contrast agent(s). The effect of particles (0–400 µg/mL) on endothelial-monocytic cell interactions in response to TNF-α was investigated using an arterial bifurcation model and dynamic monocyte adhesion assay. Spontaneous HUVEC migration (0–100 µg/mL nanoparticles) and chemotaxis of monocytic cells towards MCP-1 in presence of particles (0–400 µg/mL) were determined using a barrier assay and a modified Boyden chamber assay, respectively. Lipid nanoparticles dose-dependently reduced monocytic cell chemotaxis and adhesion to activated HUVECs. Liposomal nanoparticles had little effect on cell migration, but one formulation induced monocytic cell recruitment by HUVECs under non-uniform shear stress by about 50%. Fucoidan-coated polymer nanoparticles (25–50 µg/mL) inhibited HUVEC migration and monocytic cell chemotaxis, and had a suppressive effect on monocytic cell recruitment under non-uniform shear stress. No significant effects of iron oxide nanoparticles on monocytic cell recruitment were observed except lauric acid and human albumin-coated particles which increased endothelial-monocytic interactions by 60–70%. Some of the iron oxide nanoparticles inhibited HUVEC migration and monocytic cell chemotaxis. These nanoparticle-induced effects are of importance for vascular cell biology and function and must be considered before the potential clinical use of some of the analyzed nanosystems in cardiovascular applications.

Keywords:

• Nanoparticles
• atherothrombosis
• endothelial-monocyte interactions
• endothelial migration
• monocytic cell chemotaxis

Acknowledgements

The authors thank Prof. Beckmann (Department of Gynaecology, University Hospital Erlangen, Germany) for providing umbilical cords. We also thank Heike Kloos and Doris Flick (Laboratory of Molecular Cardiology, University Hospital Erlangen, Germany) for help with HUVEC isolation. Technical help of Julia Band is gratefully acknowledged.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the EU (‘NanoAthero’ project FP7-NMP-2012-LARGE-6-309820), the DFG (CI 162/2-1), and received the financial support from ANR-13-LAB1-0005-01 ‘FucoChem’. LETI/DTBS is part of the Arcane Labex program, funded by the French National Research Agency (ARCANE project no. ANR-12-LABX-003).