Development of nano capsules toward MR imaging agent

• Project/Area Number: 15K11232
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Osaka Dental University
• Principal Investigator: MAKITA Yoshimasa 大阪歯科大学, 歯学部, 講師 (30454573)
• Research Collaborator: OGAWA Akiya
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ヘミクリプトファン / ナノカプセル / ガドリニウム / MRI / 造影剤 / カプセル / ＭＲＩ

Outline of Final Research Achievements

Gadolinium-containing nano-capsules were synthesized and determined their structure. The obtained nano-capsules were revealed to improve the relaxivity of water compared to Gd-DTPA, mono and dinuclear gadolinium complexes. In addition, a nano-capsule bearing a tri-amide group was synthesized and determined the structure. It was clarified that an acetylcholine was encapsulated inside the cavity of nano-capsule. A nano-capsule having biphenyl linkers was synthesized and performed structure determination. It was revealed that the nano-capsule was simultaneously encapsulated three components of cobalt ion, chloroform and acetonitrile inside the cavity.

Academic Significance and Societal Importance of the Research Achievements

ガドリニウムMRI造影剤は、遊離のガドリニウムイオンが組織に沈着し肝臓・骨髄などに毒性を持つことが報告されていることから、ガドリニウムイオンの濃度を増やすことなく高感度化することが望まれている。本研究成果で得られたガドリニウム内包ナノカプセルは、ガドリニウムイオンを分子状のカプセル内部に導入した初めての例であり、水の緩和度がガドリニウムイオンの内包化により向上することを示した初めての例である。本手法がガドリニウムMRI造影剤を高感度化するための新たな選択肢となると考えられる。

Research Products

• [Journal Article] Synthesis and characterization of a biphenyl-linked hemicryptophane and an endohedral cobalt(II) complex (2017)
  • Author(s): Makita Yoshimasa、Danno Tomofumi、Ikeda Keisuke、Lee Hsien-Han、Abe Taro、Sogawa Kento、Nomoto Akihiro、Fujiwara Shin-ichi、Ogawa Akiya
  • Journal Title: Tetrahedron Letters Volume: 58 Issue: 48 Pages: 4507-4509
  • DOI: 10.1016/j.tetlet.2017.10.039
  • Peer Reviewed
• [Journal Article] A tri-aromatic amide hemicryptophane host: synthesis and acetylcholine binding (2016)
  • Author(s): Makita, Yoshimasa; Katayama, Natsuki; Lee, Hsien-Han; Abe, Taro; Sogawa, Kento; Nomoto, Akihiro; Fujiwara, Shin-ichi; Ogawa, Akiya
  • Journal Title: Tetrahedron Letters Volume: 57(46) Issue: 46 Pages: 5112-5115
  • DOI: 10.1016/j.tetlet.2016.10.017
  • Peer Reviewed
• [Journal Article] Mono- and dinuclear gadolinium(III) complexes of tris(4-carboxy-3-benzyl-3-azabutyl) amine: Synthesis and relaxation properties (2016)
  • Author(s): Yoshimasa Makita, Masashi Inoue, Natsuki Katayama, Hsien-Han Lee, Taro Abe, Chizuko Inui-Yamamoto, Yuki Mori, Yoshichika Yoshioka, Yoshitomo Honda, Shoko Gamoh, Kimishige Shimizutani, Shin-ichi Fujiwara, Akiya Ogawa
  • Journal Title: Polyhedron Volume: 107 Pages: 148-152
  • DOI: 10.1016/j.poly.2015.12.064
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] PEG官能基化ヘミクリプトファンの合成と性質 (2019)
  • Author(s): 山岡弘樹, 牧田佳真, 藤原眞一, 小川昭弥
  • Organizer: 第99回日本化学会春季年会
• [Presentation] ナノカプセル型MRイメージング剤の開発 (2016)
  • Author(s): 牧田佳真, 本田義知, 蒲生祥子, 清水谷公成, 藤原眞一
  • Organizer: 第23回日本歯科医学会総会
  • Place of Presentation: 福岡サンパレス（福岡県）
  • Year and Date: 2016-10-20