Design of functional ligand molecules focused on specific metabolism of cancer cells and their applications for diagnosis and therapy
| Project/Area Number |
15H04635
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
野本 貴大 東京工業大学, 科学技術創成研究院, 助教 (00734732)
武元 宏泰 東京工業大学, 科学技術創成研究院, 助教 (10709249)
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| Co-Investigator(Renkei-kenkyūsha) |
AOKI Ichio 量子科学技術研究開発機構, 放射線医学研究開発部門, チームリーダー (10319519)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | がん細胞 / がん代謝 / ターティング / 合成高分子 / アミノ酸トランスポーター / ターゲティング / 治療抵抗性がん / イメージング / 高分子ミセル / 光線力学治療 / 治療抵抗生がん |
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| Outline of Final Research Achievements |
In this study, we have developed a novel ligand molecule based on the common metabolic pathway to cancer cells (aberrant glutamine metabolism), using synthetic polymers. In vitro experiments confirmed that the ligand molecules, poly(amino acids) having glutamine moieties at the side chain, selectively interact with cancer cells through the multivalent binging to the glutamine transporter ASCT2 overexpressed in cancer cells. Confocal microscopic observation revealed that the ligand molecules are internalized by cancer cells, reaching lysosomal compartments. In vivo experiments demonstrated that the ligand molecules directly injected to the tumor showed longer retention compared with control ligands. These results suggest the utility of the ligand molecules as a versatile targeting technique specific to cancer cells. The novel ligand molecules are expected to be applied to cancer diagnosis and therapy.
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Report
(4 results)
Research Products
(67 results)
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[Journal Article] Sonodynamic therapy based on combined use of low dose administration of epirubicin-incorporating drug delivery system and focused ultrasound2017
Author(s)
M. Maeda, Y. Muragaki, J. Okamoto, S. Yoshizawa, N. Abe, H. Nakamoto, H. Ishii, K. Kawabata, S. Umemura, N. Nishiyama, K. Kataoka, H. Iseki
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Journal Title
Ultrasound Med. Biol.
Volume: 43
Issue: 10
Pages: 2295-2301
DOI
Related Report
Peer Reviewed
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[Journal Article] Block copolymer-boron cluster conjugate for effective boron neutron capture therapy of solid tumors.2017
Author(s)
P. Mi, H. Yanagie, N. Dewi, H.-C. Yen, X. Liu, M. Suzuki, Y. Sakurai, K. Ono, H. Takahashi, H. Cabral, K. Kataoka,
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Journal Title
J. Control. Release
Volume: 254
Pages: 1-9
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Multilayered polyion complexes with dissolvable silica layer covered by controlling densities of cRGD-conjugated PEG chains for cancer-targeted siRNA delivery.2017
Author(s)
M. Naito, R. Azuma, H. Takemoto, M. Hori, N. Yoshinaga, S. Osawa, R. Kamegawa, H. -J. Kim, T. Ishii, N. Nishiyama, K. Miyata, K. Kataoka
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Journal Title
J. Biomater. Sci. Polym.
Volume: 28
Issue: 10-12
Pages: 1109-1123
DOI
Description
【掲載確定】 in press
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Synthesis of PEGylated poly(amino acid) pentablock copolymers and their self-assembly.2016
Author(s)
Iijima, M., Ulkoski, D., Sakuma, S., Matsukuma, D., Nishiyama, N., Otsuka, H. and Scholz, C.
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Journal Title
Polym. Int.
Volume: 65
Issue: 10
Pages: 1132-1141
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Enhanced Efficacy against Cervical Carcinomas through Polymeric Micelles Physically Incorporating the Proteasome Inhibitor MG132.2016
Author(s)
Matsumoto Y, Miyamoto Y, Cabral H, Matsumoto Y, Nagasaka K, Nakagawa S, Yano T, Maeda D, Oda K, Kawana K, Nishiyama N, Kataoka K, Fujii T
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Journal Title
Cancer Sci
Volume: in press
Issue: 6
Pages: 773-781
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Calcium phosphate-based organic-inorganic hybrid nanocarriers with pH-responsive on/off switch for photodynamic therapy2016
Author(s)
T. Nomoto, S. Fukushima, M. Kumagai, K. Miyazaki, A. Inoue, P. Mi, Y. Maeda, K. Toh, Y. Matsumoto, Y. Morimoto, A. Kishimura, N. Nishiyama, K. Kataoka
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Journal Title
Biomater. Sci.
Volume: 印刷中
Issue: 5
Pages: 826-838
DOI
Related Report
Peer Reviewed
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