Nanoparticles as Contrast Agents for Optoacoustic Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 117

image contrast and quality [39], particularly in cancer research. exogenous contrast
agents are classified as nonplasmonic and as nanoparticles with sPR. Both classes
could be used as nontargeted and targeted for a variety of OA techniques including
microscopy, tomography, single wavelength, and multispectral imaging. commonly
used nonplasmonic contrast agents for PA imaging include dyes, such as Icg, various
carbon nanotubes (cNTs), quantum dots, and noble metal nanoconstructs, generally
gold nanoparticles.

5.3.1 dye-encapsulated Nanoparticles: icg, Viruses, Qds, etc.

Icg, the cyanine dye, with peak absorption at approximately 800 nm has been suc-
cessfully used as a diagnostic aid for measuring blood volume, cardiac output, and
hepatic function. It is the only fDA-approved NIR chromophore. Icg (molecular
weight of its sodium salt, M W ~ 775 Da) is an excellent NIR light absorber with
reported values of its molar extinction coefficient in aqueous media ranging between
8 × 10 4 and 1.2 × 10 5 m −1 cm −1 at 780 nm [64], which corresponds to absorption cross
section for 780 nm, of about 3 × 10 −16 to 4.6 × 10 −16 cm 2 [65, 66].
Noninvasive OA angiography with Icg has been reported in animal brains [67].
When the dye is injected into the circulation system of a rat, Icg significantly
enhances the absorption contrast between the blood vessels and the background tis-
sues. Because NIR light can penetrate deep into brain tissues through the skin and the
skull, the vascular distribution in the rat brain can be reconstructed from the OA sig-
nals with high spatial resolution and low background. It has been reported that OAT
could image objects embedded at depths of up to several centimeters at a resolution
of less than 1000 µm with a sensitivity of less than 10 pm of Icg in the blood [68].
Resolution of OA imaging has deteriorated slowly with increasing imaging depth for
this contrast agent.
A free dye Icg has a half-life of only a few minutes in the blood stream. Dye
encapsulation in nanoparticles significantly increases its circulation time [69].
Nanoparticles (~100 nm in diameter) containing Icg have been developed as a con-
trast agent for OA imaging using organically modified silicate (ormosil) as a matrix
[69]. encapsulation of the dye in the silicate matrix provided a number of benefits for
OA. first, the nanoparticle surface can be engineered for incorporating a targeting
moiety for selective contrast enhancement. second, superior contrast is achieved
because of the high dye concentration in the nanoparticle. for example, efficient
encapsulation of Icg with up to 23,000 dye molecules entrapped in a single nanopar-
ticle has been reported [69]. finally, encapsulation in a nanoparticle stabilizes Icg
dye molecules against the effects of an aqueous medium and other destabilizing
effects from the biological environment.
In addition to the silica (and polymeric shells), viruses have also been used to
encapsulate Icg [66]. In comparison to animal viruses, plant viruses are easier to pro-
duce and purify, and they are more chemically and structurally stable [70-72]. The
surface of the viruses is amenable to modification, for example, surface conjugation of
the cowpea mosaic virus (cPmV) with a folic acid-polyethylene glycol (Peg) moiety
has been achieved for in vitro recognition of tumor cells bearing a folate receptor [73].