Biomedical Engineering Reference
In-Depth Information
The transition of UCAs from protein-based microbubbles
to optimized liposomal particles containing gases that further
enhance the US signal also provides a greatly improved platform
for derivatization using specific ligands to facilitate targeting. The
two main areas that have been investigated for UCA targeting are
inflammation and cancer.
8.3.3 TargetingInfl ammation
UCAs can be actively targeted to specific tissues in two ways, by
inclusion of a targeting moiety on the one or more of the chemical
constituents of the UCA or by chemical attachment of a targeting
ligand, such as a peptide or antibody, to one of its constituents.
The size and the composition of the shell, especially in the case
of protein-based shells, will also aff ect the distribution in vivo ,
providing additional biological information. This “passive” targeting
can provide information on blood flow, the lymphatic system, or
the systems that interact with foreign agents in the body, such as
phagocytic lymphocytes. It could be argued that microbubbles with
a shell consisting of denatured albumin represent both passive
and active targeting of inflammation because the microbubble
itself provides a marker of increased vascular permeability while
the albumin shell interacts with activated endothelial cells. It has
also been noted that in some cases albumin-based microbubbles
are retained in the myocardium, leading to an enhanced US signal.
It was hypothesized that this was due to interaction between the
microbubbles and the inflamed endothelial tissue. Villanueva et al.
[33] tested this hypothesis in an in vitro study in which they found
that albumin-based microbubbles adhered strongly to the exposed
inflamed extracellular matrix of endothelial cells. In related work
also targeting inflammation, Unger et al . [34] coupled a hexapeptide
representing the minimum functional unit from fibrinogen (amino
acid sequence KQAGDV) to a lipid, incorporated the functionalized
lipid into a PFC-containing liposome, and observed increased binding
of this UCA to blood clots in vitro . Similarly, Christiansen et al. [35]
used phosphatidylserine (PS)-containing lipid microbubbles to
target leukocytes in order to quantify inflammation from myocardial
reperfusion injury. Including PS in the lipid composition increased
complement-mediated microbubble attachment to the activated
leukocytes involved in inflammation. The authors report both
 
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