Photoacoustic and Ultrasound Imaging with Nanosized Contrast Agents - Nanotechnology for Biomedical Imaging and Diagnostics - page 296

addition, gnCs were successfully utilized as a nonionizing optical lymph node
tracer for noninvasive PA mapping sentinel lymph nodes in small animals in vivo
(Fig. 10.7b) [119]. After intradermal injection of 0.2 pmol gnCs, the PA signal was
enhanced by 630%.
10.5.2 Biodegradable Plasmonic gold nanobeacons and organic
Porphysomes [115-118, 125, 126]
In spite of these promising results and biocompatibility, gnCs are not biodegradable.
The previous literature indicates that greater than 40% of intravenously injected
PEgylated gnCs accumulated in internal organs such as the livers and spleens, and
its long-term toxicity has not been studied [127, 128]. Thus, a concern regarding
long-term heavy metal poisoning is still an ongoing debate. Therefore, this may
ultimately hinder inorganic nanostructures from being used widely in clinical practice.
In contrast, organic nanoparticles (including liposomes, micelles, and polymersomes)
have been widely used in many clinical therapeutic practices due to their biocompat-
ibility, biodegradability, and drug delivery capacity [129]. Unfortunately, they are
not useful for PAT because the light absorption of these organic nanoparticles is
significantly low and thus negligible in the nIr spectral region. To enhance the
biodegradability of nanoplatforms while maintaining strong optical absorption, two
types of nanoparticles have been tested: (1) colloidal gold nanobeacons formed by a
cluster of small gold nanoparticles (~2-4 nm) coated with large phospholipid layer
(~150 nm) [115-118] and (2) porphysomes self-assembled from phospholipid-
porphyrin conjugates, providing liposome-like structure [125, 126]. In the first type,
smaller gold nanoparticles (2-4 nm) were encapsulated by soft and hollow colloidal
phospholipid particles as shown in Figure 10.8 [117]. Although gold nanobeacons
still used metallic gold nanoparticles, the size of them was small enough to be
excreted from a body. Further, gold nanobeacons strongly absorb light in both visible
and nIr regimes, and thus it can serve as a PA contrast agent. To test the in vivo PA
imaging capability of gold nanobeacons, axillary vasculatures were monitored before
and after intravenous injection of a solution of gold nanobeacons. The PA signals in
the blood vessels quantified from the PA image (Fig. 10.8b, right) acquired at 156 min
postinjection were enhanced by approximately 60% compared to that measured from
the control PA image (Fig. 10.8b, left). Thus, gold nanobeacons can be potentially
used for molecular PAT as exogenous contrast agents. In the second type, porphy-
somes are self-assembled from monomers, efficient drug delivery vehicles, highly
biodegradable, and highly biocompatible. In addition, porphysomes have strong and
tunable optical absorption coefficients and are effective agents for PAT. Figure 10.8c
shows a schematic and electron micrograph of a pyropheophorbide-lipid porphysome.
From a phantom study, PA signals could be detectable from the porphysomes at a
particle concentration of 25 pM. This detection sensitivity corresponds to approxi-
mately 50 × 10 −21 moles of porphysomes per imaging voxel. The axillary region of a rat
was photoacoustically imaged before and after intradermal injection of porphysomes
(2.3 pmol) in small animals in vivo . Secondary lymph vessels, sentinel lymph node,
and inflowing lymph vessel are clearly visible in the PA image (Fig. 10.8d).