Photoacoustic and Ultrasound Imaging with Nanosized Contrast Agents - Nanotechnology for Biomedical Imaging and Diagnostics - page 294

molecules suffer from fast circulation times, relatively small optical absorption
cross-sectional areas, and/or chemical stains. To surmount the limitations of small
molecules, more recently, gold nanostructures have been heavily investigated as
contrast agents for PAT [86-89]. nanotechnology has garnered much attention due
to its potential application in biomedicine [90-93]. nanostructure-based theranostic
systems bring many advantages: (i) the nanostructures can be functionalized using
standard procedures in nanotechnology. The type, the size, and the number of linkers
on the surface of nanostructures can be tuned according to their specific applications.
(ii) They can selectively deliver diagnostic or therapeutic agents to the disease sites
at effective concentration and consequently boost the efficacy of existing imaging
and treatment outcomes. (iii) The release kinetics of the agents or drugs can be
controlled by using internal or external manipulation. (iv) Most importantly, the
optical properties of the nanoplatforms, in the case of plasmonic gold nanostructures,
can generate excessive heating due to localized surface plasmon resonance (LSPr)
under laser irradiation [94]. This effect is known as the photothermal effect [95-98],
which considerably assists PAT and killing of tumor cells.

10.5.1 Plasmonic gold nanocages

Among many different types of gold nanostructures (e.g., gold nanoshells [99, 100],
gold nanorods [101-111], gold nanospheres [112, 113], gold nanostars [114], gold
nanobeacons [115-118], etc.), gold nanocages (gnCs) have been actively used as a PA
contrast agent due to their strong and tunable optical absorption in the nIr spectral
range, bioinertness, low heavy metal toxicity, and easiness to be functionalized the sur-
face [76, 86, 119, 120]. generally, the gnCs can be synthesized using the galvanic
replacement reaction between the Ag nanocubes and chloroauric acid in aqueous solu-
tion [121-123]. Figure 10.6 shows the optical and physical properties of gnCs. As
shown in Figure 10.6a, the LSPr peak of gnCs can be adjustable by controlling the
ratio between wall thickness and edge length via the reaction of Au nanocube solution
with different volumes of HAuCl 4 solution [122]. A TEM image of gnCs with an edge
length of 55 nm is shown in Figure 10.6b [76]. The theoretical calculation based on a
discrete dipole approximation method confirmed that gnCs were a highly absorbing
material instead of a scattering one (Fig. 10.6c) [124]. The experimentally measured
absorption cross section was approximately 6 × 10 −15 m 2 . Further, the ratio between the
absorption and extinction cross sections was 82% in both experimental and mathematical
simulation results. These results indicate that the absorption cross section of the gnCs
is 10 5 larger than that of the small dye molecules, making the gnCs ideal as a contrast
agent for PAT. From a phantom study, PA signals could be detectable from the gnCs
at a particle concentration of 4.5 pM and a Snr of 9. This detection sensitivity corre-
sponds to approximately 9 × 10 −21 moles of gnCs per imaging voxel.
As in vivo preclinical applications, gnCs conjugated with [nle 4 , d-Phe 7 ]-α-
melanocyte-stimulating hormone (MSH) was utilized to photoacoustically delineate
the boundaries of B16 melanomas in small animals in vivo (Fig. 10.7a) [76]. The
enhancement in PA signal within the melanomas reached approximately 38% with
an intravenous injection of [nle 4 , d-Phe 7 ]-α-MSH-gnCs at the dose of 1 pmol. In