バイオ応用を目指した多機能ナノカーボン材料の開発

2009 Fiscal Year Annual Research Report

• Project/Area Number: 21791929
• Research Institution: Hokkaido University
• Principal Investigator: 阿部 薫明 Hokkaido University, 大学院・歯学研究科, 助教 (40374566)
• Keywords: 歯科用材料・歯科理工学 / カーボンナノチューブ / フラーレン / 体内動態

Research Abstract

本研究では、フラーレンやカーボンナノチューブ(以下、CNT)などの炭素系ナノ微粒子(ナノカーボン)のバイオ応用の可能性を検討する為に、まずナノカーボンの親水化処理、その体内動態の可視化を試みた。
CNTのバイオ応用への第一段階として、コハク酸過酸化物との反応によりCNT表面に多数のカルボン酸を提示させること、及びその定量に成功した。反応条件の検討から、最適条件では10wt%のカルボキシル基の導入に成功した。この化学修飾により、生体への投与の為の目標としていた、数百ppmの濃度での分散も可能となり、数週間に渡り沈殿を生じずに水中へと分散することに成功した。得られたCNT誘導体をマウスへと投与し経過観察を行った(最大4週間)ところ、状態観察・体重推移などから対照群との顕著な差異は見られなかった。投与後一週間のマウスから肺・肝臓を摘出し、透過型電子顕微鏡を用い観察したところ、各臓器へのCNT誘導体の到達・滞留が確認され、投与物質が血流に乗り各臓器へと到達している事が示唆された。また、CNTの蓄積が見られた臓器(肝臓)由来の細胞を用いて、刺激性の評価を行ったところ、著しい刺激応答は観察されなかった。今回行った細胞試験・動物実験などの結果からは、CNT誘導体の生体への顕著な毒性は見られなかった。
またCNTなどナノカーボンを生体へと応用する基礎検討として、水分子とグラフェンシートとの相互作用を分子軌道計算により評価した。グラフェン上に設置した水分子はシート上を拡散し、素早くシート末端へと移動したのち、末端の水素原子との相互作用により一時的に捕捉された後、グラフェン面から遊離する事が示された。またその捕捉様式には2種類の構造が存在する事も示された。

Research Products

• [Journal Article] Interaction of water molecules with graphene : A Density Functional Theory and Molecular Dynamics study (2010)
  • Author(s): Shigeaki Abe, Yoshinori Nagoya, Fumio Watari, Hiroto Tachikawa
  • Journal Title: Japanese J.Applied.Physics 49 Pages: 01AH071-01AH074
  • Peer Reviewed
• [Journal Article] A Direct ab-initio MD study on the interaction of hydroperoxy radical(HOO)with Water Molecules (2010)
  • Author(s): Hiroto Tachikawa, Shigeaki Abe
  • Journal Title: Physical Chemistry Chemical Physics 9 Pages: 3904-3909
  • Peer Reviewed
• [Journal Article] Structure and electronic states of water molecules on nanocarbon materials : A Density Functional Theory study (2010)
  • Author(s): Shigeaki Abe, Yoshinori Nagoya, Fumio Watari, Hiroto Tachikawa
  • Journal Title: Japanese J.Applied.Physics (in press)
  • Peer Reviewed
• [Journal Article] Internal distribution of micro-/nano-sized ceramics and metals particles in mice (2010)
  • Author(s): Shigeaki Abe, Ikuhiro Kida, Mitsue Esaki, Nobuki Iwadera, Mami Mutoh, Chika Koyama, Tsukasa Akasaka, Motohiro Uo, Yoshinori Kuboki, Manabu Morita, Yoshinori Sato, Koichi Haneda, Tetsu Yonezawa, Balachan dran Jeyadevan, Kazuyuki Tohji, Fumio Watari
  • Journal Title: J.Ceramic Society of Japan (in press)
  • Peer Reviewed
• [Journal Article] Photophysical characterization of coumarin-doped poly(lactic acid)microparticles and visualization of the biodistribution (2010)
  • Author(s): Shigeaki Abe, Takayuki Kiba, Kiyotada Hosokawa, Satoru Nitobe, Takashi Hirota, Tsukasa Akasaka, Motohiro Uo, Yoshinori Kuboki, Shin-Ichiro Sato, Fumio Watari, Iosif D.Rosca
  • Journal Title: J.Electron Spectroscopy and Related Phenomena (in press)
  • Peer Reviewed
• [Journal Article] Carbon Nanotubes Chromatography separated Albumin from other Serum Proteins : A Method of direct analysis of other interactions (2010)
  • Author(s): Yoshinori Kuboki, Takamitsu Koshikawa, Hiroko Takita, Ryuichi Fujisawa, Min-ho Li, Shigeaki Abe, Tsukasa Akasaka, Motohiro Uo, Fumio Watari, Rachel L.Sammons
  • Journal Title: Dental Mater.J. 9(in press)
  • Peer Reviewed
• [Journal Article] Osteoblastic cellular responses to aluminosilicate nanotubes, imogolite using Saos-2 and MC3T3-E1 cells (2010)
  • Author(s): Kosuke Ishikawa, Shigeaki Abe, Yasutaka Yawaka, Masaya Suzuki, Fumio Watari
  • Journal Title: J.Ceramic Society of Japan 9(in press)
  • Peer Reviewed
• [Journal Article] Time-dependence and visualization of TiO_2 and Pt particle biodistribution in mice (2009)
  • Author(s): Shigeaki Abe, Chika Koyama, Motohiro Uo, Tsukasa Akasaka, Yoshinobu Kuboki, Fumio Watari
  • Journal Title: J.Nanoscience Nanotechnology 9 Pages: 4988-4991
  • Peer Reviewed
• [Journal Article] Internal distribution of several inorganic microparticles in mice (2009)
  • Author(s): Shigeaki Abe, Chika Koyama, Tsukasa Akasaka, Motohiro Uo, Yoshinori Kuboki, Fumio Watari
  • Journal Title: Key Engineering Materials 396-398 Pages: 539-542
  • Peer Reviewed
• [Journal Article] A DFT and MD study on the interaction of carbon nano-materials with metal ions (2009)
  • Author(s): Shigeaki Abe, Fumio Watari, Tomoya Takada, Hiroto Tachikawa
  • Journal Title: Molecular Crystals and Liquid Crystals 505 Pages: 289-296
  • Peer Reviewed
• [Journal Article] Controlled calcification using polyanionic macromolecules with an active reaction center analogue of carbonic anhydrase (2009)
  • Author(s): Shigeaki Abe, Tomoki Ishida, Emi Yamatoya, Daisuke Hayashi, Tsukasa Akasaka, Motohiro Uo, Fumio Watari, Tomoya Takada
  • Journal Title: Nano Biomedicine 1 Pages: 51-58
  • Peer Reviewed
• [Journal Article] Observation of Biodistribution of Indium-Tin Oxide Nanoparticles in mice (2009)
  • Author(s): Shigeaki Abe, Tetsu Yonezawa, Tsukasa Akasaka, Motohiro Uo, Fumio Uchida, Fumio Watari
  • Journal Title: Nano Biomedicine 1 Pages: 70-74
  • Peer Reviewed
• [Journal Article] Biodistribution imaging of magnetic nanoparticles in mice compared with X-ray scanning analytical microscopy and Magnetic Resonance imaging (2009)
  • Author(s): Shigeaki Abe, Ikuhiro Kida, Mitsue Esaki, Tsukasa Akasaka, Motohiro Uo, Yoshinori Sato, Balachandran Jeyadevan, Yoshinori Kuboki, Manabu Morita, Kazuyuki Tohji, Fumio Watari
  • Journal Title: Bio-Medical Materials and Engineering 19 Pages: 213-220
  • Peer Reviewed
• [Journal Article] In vivo internal diffusion of several inorganic microparticles through an oral administration (2009)
  • Author(s): Shigeaki Abe, Chika Koyama, Mitsue Esaki, Tsukasa Akasaka, Motohiro Uo, Yoshinori Kuboki, Manabu Morita, Fumio Watari
  • Journal Title: Bio-Medical Materials and Engineering 19 Pages: 221-229
  • Peer Reviewed
• [Journal Article] Synthesis and characterization of a water soluble multi-walled carbon nanotube and its biodistribution in mice (2009)
  • Author(s): Shigeaki Abe, Daisuke Hayashi, Tsukasa Akasaka, Motohiro Uo, Yoshinori Kuboki, Fumio Watari, Tomoya Takada
  • Journal Title: Nano Biomedicine 1 Pages: 143-150
  • Peer Reviewed
• [Journal Article] Development of a multiwalled carbon nanotube coated collagen dish (2009)
  • Author(s): Michiko Terada, Shigeaki Abe, Tsukasa Akasaka, Motohiro Uo, Yoshimasa Kitagawa, Fumio Watari
  • Journal Title: Dental Materials J. 28 Pages: 82-88
  • Peer Reviewed
• [Journal Article] Visualization of invasion into the body and internal diffusion of nanoparticles (2009)
  • Author(s): Fumio Watari, Shigeaki Abe, Iosif.D.Rosca, Atsuro Yokoyama, Motohiro Uo, Tsukasa Akasaka, Noriyuki. Takashi, Yasunori Totsuka, Eri.Hirata, Makoto Matsuoka, Kosuke. Ishikawa, Sachiko. Itoh, Yasutaka. Yawaka
  • Journal Title: Key Engineering Materials 396-398 Pages: 569-572
  • Peer Reviewed
• [Journal Article] Maturation of osteoblast-like SaoS2 induced by carbon nanotubes (2009)
  • Author(s): Xiaoming Li, Hong Gao, Motohiro Uo, Yoshinori Sato, Tsukasa Akasaka, Shigeaki Abe, Qingling Feng, Fuzhai Cui, Fumio Watari
  • Journal Title: Biomedical Materials 4 Pages: 15005-15012
  • Peer Reviewed
• [Journal Article] Material nanosizing effect on living organisms : non-specific, biointeractive, physical size effects (2009)
  • Author(s): Fumio Watari, Noriyuki Takashi, Atsuro Yokoyama, Motohiro Uo, Tsukasa Akasaka, Yoshinori Sato, Shigeaki Abe, Yoshinori Totsuka, Kazuyuki Tohji
  • Journal Title: J.Royal Society Interface 6 Pages: S371-S388
  • Peer Reviewed
• [Journal Article] Interaction of collagen triple-helix with carbon nanotubes : Geometric property of rod-like molecules (2009)
  • Author(s): Yoshinori Kuboki, Michiko Terada, Yoshimasa Kitagawa, Shigeaki Abe, Motohiro Uo, Fumio Watari
  • Journal Title: Bio-Medical Materials and Engineering 19 Pages: 3-9
  • Peer Reviewed
• [Journal Article] Multiwalled carbon nanotube coating on titanium (2009)
  • Author(s): Michiko Terada, Shigeaki Abe, Tsukasa Akasaka, Motohiro Uo, Yoshimasa Kitagawa, Fumio Watari
  • Journal Title: Bio-Medical Materials and Engineering 19 Pages: 45-52
  • Peer Reviewed
• [Journal Article] Adhesion of human osteoblast-like cells(Saos-2)to carbon nanotube sheets (2009)
  • Author(s): Tsukasa Akasaka, Atsuro Yokoyama, Makoto Matsuoka, Takeshi Hashimoto, Shigeaki Abe, Motohiro Uo, Fumio Watari
  • Journal Title: Bio-Medical Materials and Engineering 19 Pages: 147-153
  • Peer Reviewed
• [Journal Article] Physical properties of alminosilicate nanotubes, Imogolite, as scaffold and effect on osteoblastic mineralization (2009)
  • Author(s): Kosuke Ishikawa, Tsukasa Akasaka, Yoshinobu Nodasaka, Natsumi Ushijima, Masayuki Kaga, Shigeaki Abe, Motohiro Uo, Yasutaka Yawaka, Masaya Suzuki, Fumio Watari
  • Journal Title: Nano Biomedicine 9 Pages: 109-120
  • Peer Reviewed
• [Presentation] 各種マイクロ・ナノ粒子の体内動態の可視化と生体への影響 (2010)
  • Author(s): 阿部薫明、岩寺信喜、伊藤佐智子、大口郁子、赤坂司、宇尾基弘、久保木芳徳、亘理文夫、林大輔、高田知哉、米澤徹
  • Organizer: 第2回ナノ・バイオメディカル学会
  • Place of Presentation: 大阪大学, 吹田
  • Year and Date: 2010-02-22
• [Presentation] ナノカーボン表面からの水分子の蒸発メカニズム (2010)
  • Author(s): 阿部薫明、亘理文夫、田地川浩人
  • Organizer: 北海道支部2010年冬季研究発表会
  • Place of Presentation: 北海道大学, 札幌
  • Year and Date: 2010-01-27
• [Presentation] 有機マイクロ/ナノ粒子の体内循環挙動の追跡 (2010)
  • Author(s): 阿部薫明、林大輔、伊藤佐智子、大口郁子、赤坂司、宇尾基弘、亘理文夫、高田知哉
  • Organizer: 第23回代用臓器・再生医学研究会
  • Place of Presentation: 北海道大学, 札幌
  • Year and Date: 2010-01-23
• [Presentation] Controlled mineralization using biomimetic macromolecule with an active reaction center analogue of Carbonic Anhydrase (2009)
  • Author(s): Shigeaki Abe, Emi Yamatoya, Tomoki Ishida, Daisuke Hayashi, Ikuko Ohguchi, Tsukasa Akasaka, Motohiro Uo, Fumio Watari, Tomoya Takada
  • Organizer: 6^<th> Singapore International Chemical Conference
  • Place of Presentation: Singapore(Singapore)
  • Year and Date: 2009-12-16
• [Presentation] Internal distribution of several nano-magnetic particles in mice (2009)
  • Author(s): Shigeaki Abe, Ikuhiro Kida, M.Esaki, Tsukasa Akasaka, Motohiro Uo, Yoshinori Kuboki, Manabu Morita, Koichi Haneda, Balachandran Jeyadevan, Yoshinori Sato, Kazuyuki Tohji, Fumio Watari
  • Organizer: 9^<th> Asian BioCeramics Symposium(ABC2009)
  • Place of Presentation: Nagoya Congress Center, Nagoya
  • Year and Date: 2009-12-09
• [Presentation] Evaporation dinamics of water molecules on nanocarbon materials : A DFT and MD study (2009)
  • Author(s): Shigeaki Abe, Yoshinori Nagoya, Fumio Watari, Hiroto Tachikawa
  • Organizer: 22^<nd> International symposium of Microprocesses and Nanotechnology
  • Place of Presentation: Sheraton Hotel, Sapporo
  • Year and Date: 2009-11-19
• [Presentation] 各種マイクロ・ナノ粒子の生体内での分布状態の追跡とその可視化 (2009)
  • Author(s): 阿部薫明、岩寺信喜、武藤麻未、林大輔、大口郁子、赤坂司、宇尾基弘、亘理文夫、高田知哉、米澤徹
  • Organizer: 第30回日本バイオマテリアル学会
  • Place of Presentation: 京都テルサ, 京都
  • Year and Date: 2009-11-17
• [Presentation] Observation of internal distribution of micro/nano-sized ceramics and metals particles in mice (2009)
  • Author(s): Shigeaki Abe, Nobuki Iwadera, Mami Mutoh, Chika Koyama, Mitsue Esaki, Tsukasa Akasaka, Motohiro Uo, Manabu Morita, Yoshinori Kuboki, Koichi Haneda, Yasutaka Yawaka, Fumio Uchida, Tetsu Yonezawa, Fumio Watari
  • Organizer: 22^<nd> International Symposium on Ceramics in Medicine(Bioceramics22)
  • Place of Presentation: Daegu(South Korea)
  • Year and Date: 2009-10-28
• [Presentation] A Photophysical characterization of cumarin doped poly(lactic acid)micro particles and its fabrication for bioimaging (2009)
  • Author(s): Shigeaki Abe, Iosif D.Rosca, Takayuki Kiba, Kiyotada Hosokawa, Hirohisa Kobayashi, Satoru Nitobe, Takashi Hirota, Tsukasa Akasaka, Motohiro Uo, Yoshinori Kuboki, Shin-Ichiro Sato, Fumio Watari
  • Organizer: 11^<th> International Conference on Electronic Spectroscopy and Surface
  • Place of Presentation: Nara Prefectural New Public Hall, Nara
  • Year and Date: 2009-10-06
• [Presentation] 亜鉛-イミダゾール錯体を持つ酵素モデル化合物による石灰化反応の制御 (2009)
  • Author(s): 阿部薫明、林大輔、大和谷恵実、石田智毅、赤坂司、宇尾基弘、亘理文夫、高田知哉
  • Organizer: 第59回錯体化学討論会
  • Place of Presentation: 長崎大学, 長崎
  • Year and Date: 2009-09-26
• [Presentation] グラフェン-水相互作用に関する理論的研究 (2009)
  • Author(s): 阿部薫明、亘理文夫、田地川浩人
  • Organizer: 平成21年度第3回分子科学討論会
  • Place of Presentation: 名古屋大学, 名古屋
  • Year and Date: 2009-09-23
• [Presentation] A DFT and MD study on the interaction of nanocarbon materials with water molecules (2009)
  • Author(s): Shigeaki Abe, Yoshinori Nagoya, Fumio Watari, Hiroto Tachikawa
  • Organizer: 4^<th> International Conference on Polymer Batteries and Fuel Cells
  • Place of Presentation: Yokohama Symposia, Yokohama
  • Year and Date: 2009-08-03
• [Presentation] Reaction dynamics of chlorofluorocarbon on ice : A dynamics DFT study (2009)
  • Author(s): 阿部薫明, 亘理文夫, 田地川浩人
  • Organizer: 第22回化学反応討論会
  • Place of Presentation: 大宮ソニックシティー, 大宮
  • Year and Date: 2009-06-01
• [Presentation] 大気中でのオゾン-水クラスターについての理論的研究 (2009)
  • Author(s): 阿部薫明、赤坂司、宇尾基弘、亘理文夫、田地川浩人
  • Organizer: 平成21年度春期第53回日本歯科理工学会学術講演会
  • Place of Presentation: タワーホール船堀, 東京
  • Year and Date: 2009-04-11
• [Book] 『ナノ材料のリスク評価と安全性対策』第4章4「XSAMによるナノ粒子体内動態の可視化」 (2010)
  • Author(s): 亘理文夫(編集), 阿部薫明(分担執筆)
  • Publisher: フロンティア出版(in press)