Indocyanine Green-Labeled Polysarcosine for in Vivo Photoacoustic Tumor Imaging.
Photoacoustic (PA) imaging has been considered an attractive imaging modality for sensitive and in-depth imaging of biomolecules with a high resolution in vivo. PA imaging probes utilizing fluorescence dyes, including indocyanine green (ICG), have been proposed to enhance PA signal intensity. On the other hand, nanomicelles modified with polysarcosine (PSar), a biocompatible hydrophilic polymer, on their surface have previously achieved rapid tumor uptake, suggesting active transport of PSar into tumor tissues. Thus, we hypothesized that PSar-based materials might be utilized as diagnostic probes for targeting tumors and therefore evaluated the potential of PSar labeled with an ICG derivative, ICG-PSar, as a PA imaging probe for targeting cancer. In this study, ICG-PSars with differing molecular weights (10, 20, and 30 kDa) were synthesized. In vitro cellular uptake studies using ICG-PSar demonstrated rapid uptake in colon26 tumor cells partially via macropinocytosis-mediated endocytosis. In vivo fluorescence imaging and biodistribution study indicated that ICG-PSar30k exhibited high accumulation in the tumor (8.4% dose/g), with high tumor-to-blood ratios reaching 4.6 at 24 h post injection of the probe. Finally, in vivo PA imaging studies showed that PA signal increased in tumors (251%) but not in blood vessels, achieving high contrast tumor imaging at 24 h after ICG-PSar30k probe injection. These results suggest that ICG-PSar has potential as a tumor-targeting PA imaging probe.
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan , 606-8501.|Kyoto University Hospital , 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, Japan , 606-8507.
Kohei
K
Sano
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan , 606-8501.
Manami
M
Ohashi
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan , 606-8501.|Medical Imaging Project, Corporate R&D Headquarters, Canon Inc. , 3-30-2 Shimomaruko, 10 Ohta-ku, Tokyo, Japan , 146-8501.
Kengo
K
Kanazaki
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan , 606-8501.|Biomedical Imaging Research Center, University of Fukui , 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, Japan , 910-1193.
Akira
A
Makino
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan , 606-8501.
Ning
N
Ding
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan , 606-8501.
Jun
J
Deguchi
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan , 606-8501.
Yuko
Y
Kanada
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan , 606-8501.
Masahiro
M
Ono
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University , 46-29 Yoshida, Shimoadachi-cho, Sakyo-ku, Kyoto, Japan , 606-8501.
Hideo
0000-0002-3077-9321
H
Saji
D000818:Animals; D045744:Cell Line, Tumor; D004705:Endocytosis; D006801:Humans; D007208:Indocyanine Green; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging*; D010455:Peptides / Q000493:pharmacokinetics*; D061088:Photoacoustic Techniques; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D010455:Peptides; C015475:polysarcosine; D007208:Indocyanine Green; D012521:Sarcosine