Nanotechnology and nanomedicine in cardiovascular therapy - Biomaterials and Devices for the Circulatory System - page 249

Viral nanoparticles can also be fl uorescently labelled to high densities.
An example of this is the use of the cowpea mosaic virus (in living mouse
and chick embryos) as a probe which allows dynamic imaging of the vas-
cular endothelium for up to 72 hours and to a depth of 500 μ m (Lewis

et al. , 2006).

9.2.3 Computed tomography imaging

The most widely used contrast agents for computed tomography (CT) over
the past 25 years are iodine based (on a platform of tri-iodobenzene). These
molecules are limited in CVD by their non-specifi c distribution, brief
imaging times, extravasation and unsuitability in those with renal impair-
ment (Hainfeld et al. , 2006; Rabin et al. , 2006; Kong et al. , 2007).
Gold nanoparticles coated with PEG have nearly a fi ve times higher
attenuation level than that of Ultravist (a commonly used current CT con-
trast agent). Intravenous infusion, of these nanoparticles, into a rat model
revealed a signifi cantly longer intravascular time at four hours when com-
pared to 10 minutes for Ultravist. In addition the cardiac ventricles and
great vessels could be clearly delineated. However there was signifi cant
accumulation of these particles within the liver and spleen; the signifi cance
and fate of this is unclear (Kim et al. , 2007). However, smaller particles (1.9
± 0.1 nm) integrated with gold (obtained from Nanoprobes, Inc.) when

injected intravenously into mice displayed lower retention levels in the liver
and spleen. Futhermore blood vessels with diameters of approximately
100

m along with regions of angiogenesis were visible. There was no evi-
dence of toxicity up to 30 days after injection nor any alteration in mouse
behaviour (Hainfeld et al. , 2006). Gold nanoparticles have also been used
to visualise tumour vasculature in a mouse model with a stable imaging
window up to 24 hours post-injection (Cai et al. , 2007).
Nanoparticles used in CT imaging also include a polymer coated bismuth
sulphide unit and a Lipiodol-based agent. In a mouse model, the Bismuth-
based nanoparticle has demonstrated a fi ve-fold improved X-ray absorp-
tion compared with iodine, a circulation time of two hours and a safety
profi le comparable to iodine-based imaging agents (Rabin et al. , 2006). On
the other hand Lipiodol, a naturally occurring iodinated compound, can be
modifi ed with Pluronic F127 (copolymer poloxamer 407) to deliver a nano-
structure with a longer circulation time than commercial iodinated prepara-
tions while maintaining a similar safety profi le (Kong et al. , 2007).

μ

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9.2.4 Ultrasound imaging

Ultrasound with its advantages of good patient tolerance, low cost and
benign compression waves is established as an indispensable radiological