Biomedical Engineering Reference
In-Depth Information
8.2.3 Targeting
These last examples introduce the topic of targeting contrast
nanoparticles to tissues or diseases of interest. Some degree of
tumor targeting by nanoparticles is achieved passively because
of diff erences in tumor blood vessel structure compared with
that of normal tissues, through what is known as the enhanced
permeability and retention (EPR) eff ect [23]. More specific targeting
can be achieved either by designing the materials so that they are
sensitive to diff erences in environmental conditions, such as pH, or
by attaching targeting molecules such as peptides or antibodies to
the exterior of the macromolecule.
Optimal targets for nanoparticle targeting are on the luminal
side of blood vessels, as extravasation of macromolecules can be
slow. One case where this would be of great value is the detection
and description of atherosclerosis. The two following examples
demonstrate diff erent methods of identifying atherosclerotic plaques
with potential to rupture. Currently, atherosclerotic plaques can be
imaged using intravascular ultrasound (IV-US) or by MRI. However,
both of these methods have drawbacks, including the invasive nature
of IV-US and the long time required for MRI, because tissue movement
reduces the image quality. CT is faster and less expensive than both
of these techniques and the resolution is high enough to detect the
biological features of atherosclerosis. Danila et al. [24] encapsulated
iohexol in liposomes and then attached anti-ICAM-1 antibodies to
the liposomes to target them to inflamed vasculature. This resulted
in immunoliposomes that bind specifically to activated human
coronary artery endothelial cells in vitro . In another example, Wyss
et al . [25] coated liposomes with a peptide that binds E-selectin with
high affinity and measured their in vitro and in vivo selectivity. In an
ischemia-reperfusion injury model, increased uptake by activated
endothelial cells was observed compared with controls. In a tumor
imaging study, targeting the liposomes did not aff ect their blood
half-lives, but it did extend tumor residence of the particles.
8.2.4
CT Contrast Agent Summary
In this section, we considered the properties required of CT contrast
agents and how appropriate biomaterials are being selected. A
primary requirement for the development of targeted CT contrast
 
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