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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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In vivo fluorescent measurement of POZ-ICG derivatives with different molecular weights.(A) In vivo fluorescence imaging of tumor-bearing mice administered with POZ-ICG (left to right; P1-ICG1.1, P2-ICG1.1, P3-ICG0.9, P4-ICG0.7, P5-ICG0.8, P6-ICG1.0, and P7-ICG1.1). Dotted circles indicated the tumor regions. Scale bar units: photons/sec/cm2/steradian. (B) Tumor accumulation (%ID/g) (blue) and half-life in the blood (h) (red) of POZ-ICG.
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f2: In vivo fluorescent measurement of POZ-ICG derivatives with different molecular weights.(A) In vivo fluorescence imaging of tumor-bearing mice administered with POZ-ICG (left to right; P1-ICG1.1, P2-ICG1.1, P3-ICG0.9, P4-ICG0.7, P5-ICG0.8, P6-ICG1.0, and P7-ICG1.1). Dotted circles indicated the tumor regions. Scale bar units: photons/sec/cm2/steradian. (B) Tumor accumulation (%ID/g) (blue) and half-life in the blood (h) (red) of POZ-ICG.

Mentions: POZ-ICG derivatives were administered into the colon 26 tumor-bearing mice, and the tumor uptake and blood clearance were investigated (Fig. 2). A high tumor uptake (11–13% injected dose (ID)/g) was observed when the molecular weight of POZ was 15.8 kDa and more, indicating that this range of molecular weight is preferable for efficient tumor uptake via the EPR effect. The half-life in the blood was prolonged as the molecular weight of POZ-ICG increased. However, tumor-to-blood (T/B) ratios at 24 h after injection were more than three when the molecular weight of POZ was less than 50 kDa, which was significantly higher than those of PEG conjugated with ICG (PEG-ICG) we have previously examined (T/B ratios; 1.2 and 0.7 at 24 h post-injection for PEG-ICG (20 kDa) and PEG-ICG (40 kDa), respectively). Therefore, the potential of POZ-ICG as a PA probe for tumor diagnosis was demonstrated. In order to ensure high level of tumor uptake and tumor-to-blood ratios, we selected POZ with molecular weight of 25 and 50 kDa for subsequent experiments.


Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors
In vivo fluorescent measurement of POZ-ICG derivatives with different molecular weights.(A) In vivo fluorescence imaging of tumor-bearing mice administered with POZ-ICG (left to right; P1-ICG1.1, P2-ICG1.1, P3-ICG0.9, P4-ICG0.7, P5-ICG0.8, P6-ICG1.0, and P7-ICG1.1). Dotted circles indicated the tumor regions. Scale bar units: photons/sec/cm2/steradian. (B) Tumor accumulation (%ID/g) (blue) and half-life in the blood (h) (red) of POZ-ICG.
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Related In: Results  -  Collection

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f2: In vivo fluorescent measurement of POZ-ICG derivatives with different molecular weights.(A) In vivo fluorescence imaging of tumor-bearing mice administered with POZ-ICG (left to right; P1-ICG1.1, P2-ICG1.1, P3-ICG0.9, P4-ICG0.7, P5-ICG0.8, P6-ICG1.0, and P7-ICG1.1). Dotted circles indicated the tumor regions. Scale bar units: photons/sec/cm2/steradian. (B) Tumor accumulation (%ID/g) (blue) and half-life in the blood (h) (red) of POZ-ICG.
Mentions: POZ-ICG derivatives were administered into the colon 26 tumor-bearing mice, and the tumor uptake and blood clearance were investigated (Fig. 2). A high tumor uptake (11–13% injected dose (ID)/g) was observed when the molecular weight of POZ was 15.8 kDa and more, indicating that this range of molecular weight is preferable for efficient tumor uptake via the EPR effect. The half-life in the blood was prolonged as the molecular weight of POZ-ICG increased. However, tumor-to-blood (T/B) ratios at 24 h after injection were more than three when the molecular weight of POZ was less than 50 kDa, which was significantly higher than those of PEG conjugated with ICG (PEG-ICG) we have previously examined (T/B ratios; 1.2 and 0.7 at 24 h post-injection for PEG-ICG (20 kDa) and PEG-ICG (40 kDa), respectively). Therefore, the potential of POZ-ICG as a PA probe for tumor diagnosis was demonstrated. In order to ensure high level of tumor uptake and tumor-to-blood ratios, we selected POZ with molecular weight of 25 and 50 kDa for subsequent experiments.

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