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Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors

View Article: PubMed Central - PubMed

ABSTRACT

Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging.

No MeSH data available.


Signal intensity ratio of POZ-ICG (P14-ICG1.9, P14-ICG4.7, and P14-ICG7.8) and ICG.Blue: fluorescence intensity ratio, red: PA signal intensity ratio. Data were normalized by the signal intensity of ICG.
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f4: Signal intensity ratio of POZ-ICG (P14-ICG1.9, P14-ICG4.7, and P14-ICG7.8) and ICG.Blue: fluorescence intensity ratio, red: PA signal intensity ratio. Data were normalized by the signal intensity of ICG.

Mentions: Owing to high tumor accumulation observed in the in vivo biodistribution study, we selected P14 (50‚ÄČkDa, 5% hydrolysis ratio) conjugated with multiple ICG molecules (1.9, 4.7, and 7.8) for the subsequent experiments. First, the fluorescence intensities of each compound and ICG were measured. The fluorescence intensity of POZ-ICG was decreased, accompanied by an increase in the number of ICG molecules loaded (Fig. 4). Subsequently, the PA signal intensity was measured. Interestingly, the PA signal intensity of POZ-ICG was significantly increased with increase in the number of conjugated ICG molecules (39% increase for P14-ICG7.8) (Fig. 4) when compared under the same ICG concentration.


Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors
Signal intensity ratio of POZ-ICG (P14-ICG1.9, P14-ICG4.7, and P14-ICG7.8) and ICG.Blue: fluorescence intensity ratio, red: PA signal intensity ratio. Data were normalized by the signal intensity of ICG.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036052&req=5

f4: Signal intensity ratio of POZ-ICG (P14-ICG1.9, P14-ICG4.7, and P14-ICG7.8) and ICG.Blue: fluorescence intensity ratio, red: PA signal intensity ratio. Data were normalized by the signal intensity of ICG.
Mentions: Owing to high tumor accumulation observed in the in vivo biodistribution study, we selected P14 (50‚ÄČkDa, 5% hydrolysis ratio) conjugated with multiple ICG molecules (1.9, 4.7, and 7.8) for the subsequent experiments. First, the fluorescence intensities of each compound and ICG were measured. The fluorescence intensity of POZ-ICG was decreased, accompanied by an increase in the number of ICG molecules loaded (Fig. 4). Subsequently, the PA signal intensity was measured. Interestingly, the PA signal intensity of POZ-ICG was significantly increased with increase in the number of conjugated ICG molecules (39% increase for P14-ICG7.8) (Fig. 4) when compared under the same ICG concentration.

View Article: PubMed Central - PubMed

ABSTRACT

Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging.

No MeSH data available.