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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.

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Drug design of POZ-ICG derivatives for sensitive PA tumor imaging in this study.We evaluated the influence of (A) molecular weight of POZ-ICG, (B) hydrolysis ratio in POZ-ICG, and (C) number of ICG molecules conjugated with POZ on probe accumulation in the tumor.
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f1: Drug design of POZ-ICG derivatives for sensitive PA tumor imaging in this study.We evaluated the influence of (A) molecular weight of POZ-ICG, (B) hydrolysis ratio in POZ-ICG, and (C) number of ICG molecules conjugated with POZ on probe accumulation in the tumor.

Mentions: In this report, as shown in Fig. 1, we initially determined optimal molecular weight assuring tumor uptake via the EPR effect (Fig. 1A). Second, after partial hydrolysis of propionyl groups in POZ, the effect of hydrolysis ratio on tumor uptake was assessed (Fig. 1B). Third, we verified the relationship between the amount of ICG conjugated to POZ and tumor accumulation (Fig. 1C). Finally, we evaluated the feasibility of POZ multivalently conjugated with ICG (POZ-ICG) as a tumor-targeted probe for sensitive in vivo PA imaging.


Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors
Drug design of POZ-ICG derivatives for sensitive PA tumor imaging in this study.We evaluated the influence of (A) molecular weight of POZ-ICG, (B) hydrolysis ratio in POZ-ICG, and (C) number of ICG molecules conjugated with POZ on probe accumulation in the tumor.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Drug design of POZ-ICG derivatives for sensitive PA tumor imaging in this study.We evaluated the influence of (A) molecular weight of POZ-ICG, (B) hydrolysis ratio in POZ-ICG, and (C) number of ICG molecules conjugated with POZ on probe accumulation in the tumor.
Mentions: In this report, as shown in Fig. 1, we initially determined optimal molecular weight assuring tumor uptake via the EPR effect (Fig. 1A). Second, after partial hydrolysis of propionyl groups in POZ, the effect of hydrolysis ratio on tumor uptake was assessed (Fig. 1B). Third, we verified the relationship between the amount of ICG conjugated to POZ and tumor accumulation (Fig. 1C). Finally, we evaluated the feasibility of POZ multivalently conjugated with ICG (POZ-ICG) as a tumor-targeted probe for sensitive in vivo PA imaging.

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.


Related in: MedlinePlus