Historical Perspective on Nanoparticles in Imaging from 1895 to 2000 - Nanotechnology for Biomedical Imaging and Diagnostics - page 16

Targeting group

1-200 nm

Crossed-linked
protein

Filling gas

Lipids

Protecting shell

Polymer

0.5-10 µm

figure 1.11 Schematic of a microbubble with a protecting shell and targeting groups.
(Based on ref. [68].)

the bubble due to the low solubility of perfluorinated molecules in the blood. The
high stability of the microbubbles allowed imaging at much lower dosages and with
longer imaging time. In addition, these new-generation microbubbles such as Optison
(Mallinckrodt, Inc.) were approved by the fDa in 1997 and were much smaller with
diameters less than 4 µm, allowing for the imaging of the whole heart.

1.8 maturity: nanoParticles surface modifications
(late 1980s-early 2000s)

By the middle of 1980s, several imaging techniques became suitable for the identifica-
tion of internal organ pathologies. The ability to perform diagnostics noninvasively
had a profound effect on the practice of medicine. New contrast agents became com-
mercialized and rapidly adopted by clinics, which further accelerated the search for
new contrast agents including nanoparticles. However, the available methods and
contrast agents to highlight pathological changes could not be utilized for early
diagnostics, where the change in signal was often below the resolution of the instru-
mentation. furthermore, practically all types of nanoparticles were removed rapidly
from circulation by phagocytic cells of the reticuloendothelial system (reS). as a
result, nanoparticles mostly resided in the liver and the spleen. The effect of the
reS could have been hypothetically evaded by using large doses of nanoparticles or
pharmacological interventions to inactivate macrophages, but such strategies could
compromise the immune system of patients [73]. Thus, a realization emerged that
nanoparticles should be modified to alter their clearance pathway and directed
(targeted) to specific tissues.

1.8.1 targeting of nanoparticles

By the middle of the 1970s, liposomes have been the most advanced type of nanopar-
ticles and presented an excellent scaffold for the incorporation of different types of
molecules including multiple targeting moieties from small molecules to antibodies.