Evaluation of Uptake and Transport of Ultrasmall Superparamagnetic Iron Oxide Nanoparticles by Human Brain-Derived Endothelial Cells

Abstract

Aim: Ultrasmall superparamagnetic iron oxide nanoparticles (USPIO-NPs) are under development for imaging and drug delivery; however, their interaction with human blood–brain barrier models is not known. Materials & Methods: The uptake, reactive oxygen species production and transport of USPIO-NPs across human brain-derived endothelial cells as models of the blood–brain tumor barrier were evaluated for either uncoated, oleic acid-coated or polyvinylamine-coated USPIO-NPs. Results: Reactive oxygen species production was observed for oleic acid-coated and polyvinylamine-coated USPIO-NPs. The uptake and intracellular localization of the iron oxide core of the USPIO-NPs was confirmed by transmission electron microscopy. However, while the uptake of these USPIO-NPs by cells was observed, they were neither released by nor transported across these cells even in the presence of an external dynamic magnetic field. Conclusion: USPIO-NP-loaded filopodia were observed to invade the polyester membrane, suggesting that they can be transported by migrating angiogenic brain-derived endothelial cells.

Keywords::

• cell uptake
• electron microscopy
• human brain-derived endothelial cells
• iron oxide nanoparticles
• magnetic enhancement
• oxidative stress
• transcellular transport

Financial & competing interests disclosure

This work was supported by grants from the Swiss National Scientific Research Foundation (grant No 3152A0–105705) and the European Community 7^th Framework Program project project No 2007–201335 ‘NanoTest‘. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors would like to thank Bilanicova D and Marcomini A from University ‘Ca Foscari’ of Venice for providing zeta potential of uncoated USPIO-NPs.

Additional information

Funding

This work was supported by grants from the Swiss National Scientific Research Foundation (grant No 3152A0–105705) and the European Community 7^th Framework Program project project No 2007–201335 ‘NanoTest‘. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.