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CD44 Targeting Magnetic Glyconanoparticles for Atherosclerotic Plaque Imaging

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Abstract

Purpose

The cell surface adhesion molecule CD44 plays important roles in the initiation and development of atherosclerotic plaques. We aim to develop nanoparticles that can selectively target CD44 for the non-invasive detection of atherosclerotic plaques by magnetic resonance imaging.

Methods

Magnetic glyconanoparticles with hyaluronan immobilized on the surface have been prepared. The binding of these nanoparticles with CD44 was evaluated in vitro by enzyme linked immunosorbent assay, flow cytometry and confocal microscopy. In vivo magnetic resonance imaging of plaques was performed on an atherosclerotic rabbit model.

Results

The magnetic glyconanoparticles can selectively bind CD44. In T2* weighted magnetic resonance images acquired in vivo, significant contrast changes in aorta walls were observed with a very low dose of the magnetic nanoparticles, allowing the detection of atherosclerotic plaques. Furthermore, imaging could be performed without significant delay after probe administration. The selectivity of hyaluronan nanoparticles in plaque imaging was established by several control experiments.

Conclusions

Magnetic nanoparticles bearing surface hyaluronan enabled the imaging of atherosclerotic plaques in vivo by magnetic resonance imaging. The low dose of nanoparticles required, the possibility to image without much delay and the high biocompatibility are the advantages of these nanoparticles as contrast agents for plaque imaging.

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Abbreviations

DLS:

Dynamic light scattering

ELISA:

Enzyme linked immunosorbent assay

FITC:

Fluorescein isothiocyanate

FSPGR:

Fast spoiled gradient recalled

HA:

Hyaluronan

IL:

Interleukin

LDL:

Low density lipoprotein

mAb:

Monoclonal antibody

MRI:

Magnetic resonance imaging

NPs:

Nanoparticles

ROI:

Region of interest

siRNA:

Small interfering RNA

SPION:

Superparamagnetic iron oxide nanoparticle

TEM:

Transmission electron microscopy

TNF-α:

Tumor necrosis factor-α

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Acknowledgments and Disclosures

Mohammad H. El-Dakdouki, Kheireddine El-Boubbou and Medha Kamat contributed equally to this work. We would like to thank the Department of Radiology, Michigan State University for the very generous support towards access of the MRI scanner.

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Authors and Affiliations

  1. Department of Chemistry, Michigan State University, Chemistry Building, Room 426, 578 S. Shaw Lane, East Lansing, Michigan, 48824, USA

    Mohammad H. El-Dakdouki, Kheireddine El-Boubbou, Medha Kamat & Xuefei Huang

  2. Department of Medicine, Division of Cardiology, Michigan State University, East Lansing, Michigan, 48824, USA

    Ruiping Huang & George S. Abela

  3. Department of Pathobiology and Diagnostic Investigation, Michigan State University, 4125 Beaumont Road, Lansing, Michigan, 48910, USA

    Matti Kiupel

  4. Departments of Radiology and Psychology, Michigan State University, East Lansing, Michigan, 48824, USA

    David C. Zhu

Authors
  1. Mohammad H. El-Dakdouki
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  2. Kheireddine El-Boubbou
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  3. Medha Kamat
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  4. Ruiping Huang
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Correspondence to David C. Zhu or Xuefei Huang.

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El-Dakdouki, M.H., El-Boubbou, K., Kamat, M. et al. CD44 Targeting Magnetic Glyconanoparticles for Atherosclerotic Plaque Imaging. Pharm Res 31, 1426–1437 (2014). https://doi.org/10.1007/s11095-013-1021-8

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