Biomedical Engineering Reference
In-Depth Information
fluorescent dye into a strong PA contrast material [144]. Figure 10.11a shows the
schematic of PFC nanoparticles loaded with an nIr dye, pyrrolopyrrole cyanine
(PPCy-C8), and the chemical structure of the dye. Specially, PFC is biocompatible
and has a half-life of 3 days in the body. Thus, PFC can completely be removed
from the body via expired air. From
in vitro
studies, PPCy-C8-loaded PFC nanopar-
ticles produced a significantly stronger PA signal (~9 times) compared to whole
blood, while no and significantly lower PA signals were generated from pure PFC
nanoparticles and free dye, respectively. As an
in vivo
preclinical application,
PPCy-C8-loaded PFC nanoparticles were successfully used as a PA lymph node
tracer. Lymph nodes were detected by PAT at 3 h postinjection with a PA contrast
of 8.7, and the contrast was enhanced to 12.3 at 24 h postinjection. FL imaging was
also performed.
In vivo
FL intensity and FL lifetime imaging of lymph nodes with
injection of the PPCy-C8-loaded PFC nanoparticles are shown in Figure 10.11b
and c. The FL intensity with dye-loaded PFC nanoparticles was approximately 10
times lower than that with the free dye. FL lifetime of free PPCy-C8 in the lymph
node was greater than 3 ns, while that of the dye-loaded PFC nanoparticles was
0.22 ns. This result implies that the FL property of the dye was quenched in the
PFC nanoparticles.
Further, this type of dual-modality PA and FL imaging contrast agent can be
physiologically activated, referred to as an activatable PA probe. Figure 10.12a
shows the diagram of gnCs and organic dye molecules (FITC) connected together
through an enzyme-cleavable peptide [146]. To fabricate the matrix metalloprote-
ase (MMP)-sensitive agent, a FITC-labeled C-terminus peptide was conjugated to
the surface of gnCs. By controlling the LSPr peak of the gnCs (770 nm) away
from the FL emission wavelength of the dye molecule, the FL light emitted from
the released dyes was detected with high sensitivity. The FL quenching efficiency
for the dye was high. Prior to enzyme cleavage, the FL intensity of the solution was
18. After incubation with MMP-2 enzyme for 3 h, the FL dramatically increased to
69. As another approach, Levi
et al
. developed an activatable PA probe combining
two separate organic molecules having two distinct optical absorption peaks
(Fig. 10.12b) [145]. When the linker between two dyes was cleaved by the MMP-2
enzyme, the dye conjugated with cell-penetrating peptide (CPP) stayed in cells,
whereas the other one diffused away. The first dye was BHQ3 with an absorption
wavelength of 672 nm and an extinction coefficient of 42,700 M
−1
cm
−1
, while the
second one was Alex 750 with an excitation wavelength of 749 nm and an extinction
coefficient of 290,000 M
−1
cm
−1
. Before cleavage, strong PA signals were generated
from the conjugate, BHQ3-activatable photoacoustic probe-Alex 750 (B-APP-A),
at both 650 and 750 nm. After the linker was cleaved by MMP-2 enzyme, a strong
PA signal was observed at 650nm. The subtracted PA image (i.e., PA image
acquired at 650 nm—PA image obtained at 750 nm) clearly visualized the enzymatic
process (Fig. 10.12c). As another successful activatable contrast agent, aforemen-
tioned porphysomes have significant photoswitching capability between PA and
FL properties. Intact porphysomes are quenched but can become fluorescent upon
dissociation. The nanoscale photoswitching is significant, with 1000-fold FL
increase per particle [126].
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