Preferential Tumor Accumulation of Polyglycerol Functionalized Nanodiamond Conjugated with Cyanine Dye Leading to Near‐Infrared Fluorescence In Vivo Tumor Imaging |
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Authors: | Fumi Yoshino Tsukuru Amano Yajuan Zou Jian Xu Fuminori Kimura Yoshio Furusho Tokuhiro Chano Takashi Murakami Li Zhao Naoki Komatsu |
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Affiliation: | 1. Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta, Otsu, 520‐2192 Japan;2. Graduate School of Human and Environmental Studies, Kyoto University, Sakyo‐ku, Kyoto, 606‐8501 Japan;3. Department of Chemistry, Shiga University of Medical Science, Seta, Otsu, 520‐2192 Japan;4. Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Seta, Otsu, 520‐2192 Japan;5. State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD‐X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, 215123 ChinaE‐mail: ,;6. https://orcid.org/0000-0003-3249-7173;7. Graduate School of Human and Environmental Studies, Kyoto University, Sakyo‐ku, Kyoto, 606‐8501 JapanE‐mail: , |
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Abstract: | Preferential accumulation of nanoparticles in a tumor is realized commonly by combined effects of active and passive targeting. However, passive targeting based on an enhanced permeation and retention (EPR) effect is not sufficient to observe clear tumor fluorescence images in most of the in vivo experiments using tumor‐bearing mice. Herein, polyglycerol‐functionalized nanodiamonds (ND‐PG) conjugated with cyanine dye (Cy7) are synthesized and it is found that the resulting ND‐PG‐Cy7 is preferentially accumulated in the tumor, giving clear fluorescence in in vivo and ex vivo fluorescence images. One of the plausible reasons is the longer in vivo blood circulation time of ND‐PG‐Cy7 (half‐life: 58 h determined by the pharmacokinetic analysis) than that of other nanoparticles (half‐life: <20 h in most of the previous reports). In a typical example, the fluorescence intensity of tumors increases due to continuous tumor accumulation of ND‐PG‐Cy7, even more than one week postinjection. This may be owing to the stealth effect of PG that was reported previously, avoiding recognition and excretion by reticuloendothelial cells, which are abundant in liver and spleen. In fact, the fluorescence intensities from the liver and spleen is similar to those from other organs, while the tumor exhibits much stronger fluorescence in the ex vivo image. |
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Keywords: | EPR effect nanodiamonds polyglycerol stealth effect tumor imaging |
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