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Force Dependent Internalization of Magnetic Nanoparticles Results in Highly Loaded Endothelial Cells for Use as Potential Therapy Delivery Vectors

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Abstract

Purpose

To investigate the kinetics, mechanism and extent of MNP loading into endothelial cells and the effect of this loading on cell function.

Methods

MNP uptake was examined under field on/off conditions, utilizing varying magnetite concentration MNPs. MNP-loaded cell viability and functional integrity was assessed using metabolic respiration, cell proliferation and migration assays.

Results

MNP uptake in endothelial cells significantly increased under the influence of a magnetic field versus non-magnetic conditions. Larger magnetite density of the MNPs led to a higher MNP internalization by cells under application of a magnetic field without compromising cellular respiration activity. Two-dimensional migration assays at no field showed that higher magnetite loading resulted in greater cell migration rates. In a three-dimensional migration assay under magnetic field, the migration rate of MNP-loaded cells was more than twice that of unloaded cells and was comparable to migration stimulated by a serum gradient.

Conclusions

Our results suggest that endothelial cell uptake of MNPs is a force dependent process. The in vitro assays determined that cell health is not adversely affected by high MNP loadings, allowing these highly magnetically responsive cells to be potentially beneficial therapy (gene, drug or cell) delivery systems.

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Abbreviations

BAEC:

bovine aortic endothelial cell

DLS:

dynamic light scattering

FBS:

fetal bovine serum

MNP:

magnetic nanoparticles

PBS:

phosphate buffered saline

PLA:

poly(lactic acid)

PVA:

poly(vinyl alcohol)

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Acknowledgments & Disclosures

This study was partially supported by Award Number R01HL107771 from the National Heart, Lung, And Blood Institute and by Award Number F31 GM086128-01 from National Institute of General Medical Sciences supporting Cristin MacDonald’s PhD program through Ruth Kirschstein Research Service Award (RSA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the “National Heart, Lung, And Blood Institute or the National Institutes of Health.” Authors thank Dr. Robert Levy from the Children’s Hospital of Philadelphia for his generous gift of the poly(lactide) covalently labeled with BODIPY® 564/570 (Life TechnologiesTM) and Richard Sensenig from the Department of Surgery, Drexel University College of Medicine for reviewing the manuscript and providing constructive suggestions.

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Authors and Affiliations

  1. School of Biomedical Engineering, Drexel University, Philadelphia, Pennsylvania, 19104, USA

    Cristin MacDonald, Kenneth Barbee & Boris Polyak

  2. Department of Surgery, Drexel University College of Medicine, 245 N. 15th Street, NCB Suite 7150, Mail Stop 413, Philadelphia, Pennsylvania, 19102, USA

    Boris Polyak

Authors
  1. Cristin MacDonald
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  2. Kenneth Barbee
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  3. Boris Polyak
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Correspondence to Boris Polyak.

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MacDonald, C., Barbee, K. & Polyak, B. Force Dependent Internalization of Magnetic Nanoparticles Results in Highly Loaded Endothelial Cells for Use as Potential Therapy Delivery Vectors. Pharm Res 29, 1270–1281 (2012). https://doi.org/10.1007/s11095-011-0663-7

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  • DOI: https://doi.org/10.1007/s11095-011-0663-7

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