Nanomaterials for Medical Imaging …
377
vein on xenografted breast tumor on nude mice and imaged at 10, 30, 120, and 300 s.
These NBs injected at a concentration of 150 μL showed higher contrast in liver
and tumor in a time interval of 30 s possess longer imaging time compared to Sono
Vue. Apart from the size of NBs, coating over the surface of particles plays a major
role in US imaging. Initial reports with nanobubbles have been coated with either
anionic or cationic molecules. Biological interaction with these coated NBs toxicity
and cellular uptake was evaluated by Pan et al. in 2012 [265]. The toxicity of NBs
was evaluated by the assessment of biomarkers from liver and kidneys such as γglutamyl transferase (γ -GT) and blood urea nitrogen (BUN). A significant toxicity
effect in the liver compared to kidney cells, and they showed that toxicity evaluation
with biomarkers is more sensitive.
In general, contrast-enhanced ultrasound imaging requires the nanobubbles with
size less than 500 nm for increased EPR effects in the tumor area. But the serious
concerns with intravenous injection in rodents the existence of nanobubble possess
half-life less than 30 min. Mai et al. developed peptide conjugated NBs -Cyanine
5.5 NIR dye as a dual-modal imaging agent for effective uptake of nanoparticles
in tumor regime [266]. Liver cancer cells H22 were injected intraperitoneally as
a tumor model for dual imaging. US Imaging was performed in both 5 MHz and
12 MHz probe, but the higher frequency probe has much contrast enhancement in
tissues. NBs were injected intravenously at a concentration of 4 μL and acquired
using 12 MHz thyroid US probe recorded within 4 h. Ultrasound with nanobubbles
delineated a white boundary of the dark tumor region on either side of tumor and
confirmed with fluorescence imaging. Results showed that nanobubbles could be used
for subcutaneous tumor imaging with US for 2 h and gradually decreases. The next
generation of NBs for tumor imaging and therapy was developed Huang et al. in 2013,
incorporating SPIONs into nanobubbles [267]. Nanobubbles with SPIONs, dualmodal imaging, acquire images in both ultrasound and MRI. Magnetically triggered
SPIONs-NBs loaded with an anti-cancer drug are exposed to high intensity focused
ultrasound (HIFU) for the effective release of drugs. Contrast-enhanced ultrasound
is used to observe the glioma injected in the right hind limb. Magnetically guided
nanomaterials have been a keen interest due to its increased level of accumulation
in the desired target. The same group has strategically disrupted BBB via HIFU
to increase the delivery of nanomaterials in a tumor region and imaged with MRI
[268]. Mixed ratio of phospholipids functionalized with biotin containing octa-fluoro
propane C 3 F 8 gas to form NBs facilitated with anti-prostrate specific membrane
antigen [269]. Three animal xenograft models (LNCaP, C4-2, and MKN45) were
imaged using various US parameters such as peak intensity and contrast enhancement
over time. Compared to non-targeted NBs and tissues imaging without NBs, the
contrast with targeted NBs, the US parameters are higher than others.
Li et al. have demonstrated that biodegradable photoluminescent polymers can
encapsulate liquid tetra-decafluorohexane (C 6 F 14 ) through emulsion evaporation
process conjugated with neuropeptide YY 1. These neuropeptides YY1 conjugate
with Y 1 R s overexpressed in breast cancer cell lines without affecting normal
cells. Xenografted 4T1 cells were injected with BPC-NB-PNBL-NPY (50, 100, or
200 kg mg
−1 ) and were used for in vivo US imaging. Intravenous injected NBs
377
vein on xenografted breast tumor on nude mice and imaged at 10, 30, 120, and 300 s.
These NBs injected at a concentration of 150 μL showed higher contrast in liver
and tumor in a time interval of 30 s possess longer imaging time compared to Sono
Vue. Apart from the size of NBs, coating over the surface of particles plays a major
role in US imaging. Initial reports with nanobubbles have been coated with either
anionic or cationic molecules. Biological interaction with these coated NBs toxicity
and cellular uptake was evaluated by Pan et al. in 2012 [265]. The toxicity of NBs
was evaluated by the assessment of biomarkers from liver and kidneys such as γglutamyl transferase (γ -GT) and blood urea nitrogen (BUN). A significant toxicity
effect in the liver compared to kidney cells, and they showed that toxicity evaluation
with biomarkers is more sensitive.
In general, contrast-enhanced ultrasound imaging requires the nanobubbles with
size less than 500 nm for increased EPR effects in the tumor area. But the serious
concerns with intravenous injection in rodents the existence of nanobubble possess
half-life less than 30 min. Mai et al. developed peptide conjugated NBs -Cyanine
5.5 NIR dye as a dual-modal imaging agent for effective uptake of nanoparticles
in tumor regime [266]. Liver cancer cells H22 were injected intraperitoneally as
a tumor model for dual imaging. US Imaging was performed in both 5 MHz and
12 MHz probe, but the higher frequency probe has much contrast enhancement in
tissues. NBs were injected intravenously at a concentration of 4 μL and acquired
using 12 MHz thyroid US probe recorded within 4 h. Ultrasound with nanobubbles
delineated a white boundary of the dark tumor region on either side of tumor and
confirmed with fluorescence imaging. Results showed that nanobubbles could be used
for subcutaneous tumor imaging with US for 2 h and gradually decreases. The next
generation of NBs for tumor imaging and therapy was developed Huang et al. in 2013,
incorporating SPIONs into nanobubbles [267]. Nanobubbles with SPIONs, dualmodal imaging, acquire images in both ultrasound and MRI. Magnetically triggered
SPIONs-NBs loaded with an anti-cancer drug are exposed to high intensity focused
ultrasound (HIFU) for the effective release of drugs. Contrast-enhanced ultrasound
is used to observe the glioma injected in the right hind limb. Magnetically guided
nanomaterials have been a keen interest due to its increased level of accumulation
in the desired target. The same group has strategically disrupted BBB via HIFU
to increase the delivery of nanomaterials in a tumor region and imaged with MRI
[268]. Mixed ratio of phospholipids functionalized with biotin containing octa-fluoro
propane C 3 F 8 gas to form NBs facilitated with anti-prostrate specific membrane
antigen [269]. Three animal xenograft models (LNCaP, C4-2, and MKN45) were
imaged using various US parameters such as peak intensity and contrast enhancement
over time. Compared to non-targeted NBs and tissues imaging without NBs, the
contrast with targeted NBs, the US parameters are higher than others.
Li et al. have demonstrated that biodegradable photoluminescent polymers can
encapsulate liquid tetra-decafluorohexane (C 6 F 14 ) through emulsion evaporation
process conjugated with neuropeptide YY 1. These neuropeptides YY1 conjugate
with Y 1 R s overexpressed in breast cancer cell lines without affecting normal
cells. Xenografted 4T1 cells were injected with BPC-NB-PNBL-NPY (50, 100, or
200 kg mg
−1 ) and were used for in vivo US imaging. Intravenous injected NBs