Nanotechnology and nanomedicine in cardiovascular therapy - Biomaterials and Devices for the Circulatory System - page 250

tool. Its use has become widespread in most healthcare settings, leading to
increasing interest in improving ultrasound effi cacy through the introduc-
tion of micro- and nanoparticle-based agents. Microbubbles have been
used in cardiovascular imaging as they produce an acoustic signal in an
ultrasound fi eld, thereby allowing assessment of perfusion. Smaller parti-
cles such as liquid-fi lled nanodroplets may have an important role. These
nanoparticless have shown promising results in imaging microvasculature
(to 100 m). However, ultrasound imaging is less sensitive to liquid-fi lled

nanoparticles due to their size and relative incompressibility when com-
pared with microbubbles (Dayton et al. , 2006). As microbubbles and nano-
droplets have their own specifi c advantages, parallel development of both
particle families continues. For example, gas-fi lled microspheres and liq-
uid-fi lled nanoparticles may be employed in ultrasound molecular imaging
by the incorporation of surface receptor-specifi c ligands. Such particles
may be used in microvascular imaging to detect upregulated leukocyte
adhesion molecules as in ischaemia reperfusion (Weber and Lemor, 2004;
Kaufmann and Lindner, 2007; Kaufmann et al. , 2007; Villanueva and
Wagner, 2008).

μ

9.2.5 Magnetic resonance imaging

The non-invasive nature, high resolution and contrast of magnetic reso-
nance imaging (MRI) along with lack of ionising radiation have led to its
wide use in the clinical setting. Therefore considerable interest has been
generated in investigating the feasibility of utilising nanoparticles to improve
MRI (Cyrus et al. , 2005; Mulder and Fayad, 2008).
Magnetic particles have the ability to respond to variations in magnetic
fi elds and this characteristic makes them ideal candidates in the develop-
ment of nanostructures in MRI. Superparamagnetic iron oxide particles
have several possible clinical applications including the detection of metas-
tases and in infl ammatory diseases. Superparamagnetic iron oxide particles
have been combined with Annexin V (which recognises apoptotic cells via
phosphatidyl serine) to create a targeted nanoparticle which has been suc-
cessfully used to identify high grade atherosclerotic regions. In a rabbit
model of atherosclerosis this nanoparticle displayed negative MRI contrast
at atheromatous lesions but not at healthy arterial sites nor in healthy con-
trols. The dose of targeted nanoparticle required was in the order of a
thousand times less than for untargeted superparamagnetic nanoparticles
with recognisable differences between occlusive and mural plaques. Plaque
contrast is maintained for two months; however, this is undesirable in
patients requiring regular repeat MRI to assess disease progression (Smith
et al. , 2007). It is postulated that iron oxide nanoprobes may also be used
to label macrophages which can then be tracked to sites of atherosclerosis.

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