Cardiovascular diseases are the leading cause of mortalities in the world. The fact that 60% of the annual cardiac deaths reported in the USA resulted from sudden deaths with no previously diagnosed cardiac-associated pathology implies that the currently applied methods for the detection of atherosclerosis  are not effective. Thus, there is an immense need for the development of new non-invasive diagnostic methods for the detection of vulnerable atherosclerotic plaques. It has been reported recently that atherosclerotic cholesterol crystals form at the onset of atherosclerosis, and contribute to the plaque instability by inducing inflammation and mechanically rupturing the fibrous cap, thus causing heart attacks and strokes. So far, no methods are available to image cholesterol crystals non-invasively in vivo. We developed �-cyclodextrin-coated superparamagnetic iron oxide nanoparticles (�-CD-SPION) for the selective binding and non-invasive detection of cholesterol crystals in atherosclerotic plaques using Magnetic Resonance Imaging (MRI). The ability of �-CD-SPION to selectively bind to cholesterol crystals was assessed by competitive enzyme-linked immunosorbent assay (ELISA), Prussian blue staining and confocal microscopy imaging where �-CD-SPION, not the bare SPION, displayed a selective, dose dependent, and high avidity binding profile to cholesterol crystals. The collective analysis of those experiments demonstrated the significance of molecular recognition between the �-CD and cholesterol crystals to achieve selective binding and detection by MRI. In an attempt to mimic in vivo conditions and test the selectivity of �-CD-SPION in a biological system, several ex vivo staining experiments were conducted, and the binding of the NPs with  atherosclerotic rabbit aorta tissue was assessed. For example, unlike the bare SPIONs, �-CD-coated nanoparticles were found to bind extensively to the atherosclerotic lesions of the tissue as evidenced by Prussian blue staining and Transmission Electron Microscopy (TEM). To the best of our knowledge, this is the first time such a system became available for molecular imaging of cholesterol crystals.

Iron oxide based nanoparticles as selective MR contrast agents for the detection of atherosclerotic cholesterol crystals

244th National Meeting (2012)

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