Development of a New DDS Imaging Method for Visualizing Biocompatible Polymer Probes
| Project/Area Number |
16K01935
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YAMADA Hisatsugu 徳島大学, 大学院社会産業理工学研究部(生物資源産業学域), 講師 (80512764)
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| Co-Investigator(Kenkyū-buntansha) |
近藤 輝幸 京都大学, 工学研究科, 教授 (20211914)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 生体適合性ポリマープローブ / DDS / 生体イメージング / 分子プローブ / 放射線増感 / 磁気共鳴イメージング / 双性イオン型ポリマー / 薬物送達 / 分子イメージング / 生体適合性ポリマー / 生体材料 / 可視化 / 画像 / 薬剤反応性 / 高分子合成 |
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| Outline of Final Research Achievements |
In this research, we have tried to develop a new DDS imaging method using self-traceable zwitterionic polymer probe and multiple-resonance MRI. We have already developed a self-traceable phosphorylcholine polymer (PMPC) probe which forms EPR-relevant, compact nanoparticles and accumulates effectively and selectively in tumor in mice, as revealed by multiple-resonance MRI. In order to shed light on the structure-activity relationship of PMPC, we pay attention to related zwitterionic polymer probes having carboxybetaine (PMCB) or sulfobetaine (PMSB). Physicochemical and pharmacokinetic studies on these probes revealed that PMSB exhibits far less pronounced tumor selectivity for mice, as compared with PMPC and PMCB. This work suggests that selection of betaine type is important for the tumor selectivities of the polymers. We also revealed that a zwitterionic copolymer with a radio-sensitizing unit significantly enhances the radiation sensitivity of tumor in tumor-bearing chicken eggs.
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| Academic Significance and Societal Importance of the Research Achievements |
DDSに利用されるポリマーのほとんどは非イオン性のPEGを基盤としており、生体適合性に優れた双性イオンポリマーの腫瘍集積能に及ぼす因子については未解明であった。本研究から、双性イオンポリマーのマウス体内動態と腫瘍選択性は、細胞膜脂質の末端構造に特徴的な機能ではなく、側鎖の双性イオン対の組み合わせ・種類に大きく依存することが明らかとなった。これにより、腫瘍選択性および腫瘍集積性に優れた双性イオンポリマーを基軸としたDDSイメージング材料を開発する上で重要な分子設計指針が得られた。この知見が、腫瘍の診断と治療を同時に達成する腫瘍DDSイメージングの新材料の開発に繋がると期待される。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Concentration-dependent, Activation of Inflammatory/Anti-inflammatory Functions of Macrophages by Hydrolyzed Whey Protein2018
Author(s)
Toru Tasaka, Emi Kuwada, Yuka Izuchi, Ryohei Nishigawa, Hisatsugu Yamada, Hideki Unuma, Ken Tokunaga, Akio Hayakawa, Akiteru Go, Kikyo Go, and Yoshihiro Uto
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Journal Title
Anticancer Res.
Volume: 38
Pages: 4299-4304
Related Report
Peer Reviewed
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[Journal Article] Development of a novel Schiff base derivative for enhancing the anticancer potential of 5-aminolevulinic acid-based photodynamic therapy.2017
Author(s)
Shinohara Y, Endo Y, Abe C, Shiba I, Ishizuka M, Tanaka T, Yonemura Y, Ogura SI, Tominaga M, Yamada H, Uto Y.
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Journal Title
Photodiagnosis Photodyn Ther
Volume: 20
Pages: 182-188
DOI
Related Report
Peer Reviewed
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[Journal Article] 5-Aminolevulinic Acid Enhances Ultrasound-Mediated Antitumor Activity via Mitochondrial Oxidative Damage in Breast Cancer2016
Author(s)
Shimamura, Y.; Tamatani, D.; Kuniyasu, S.; Mizuki, Y.; Suzuki, T.; Katsura, H.; Yamada, H.; Endo, Y.; Osaki, T.; Ishizuka, M.; Tanaka, T.; Yamanaka, N.; Kurahashi, T.; Uto, Y.
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Journal Title
Anticancer Res.
Volume: 36
Pages: 3607-3612
Related Report
Peer Reviewed
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