Cell Nanoengineering: Control of Cell Functions by External Stimuli-Responsive Nanomaterials Delivered to Specific Organelle

• Project/Area Number: 24300162
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Kyoto University
• Principal Investigator: Murakami Tatsuya 京都大学, 物質－細胞統合システム拠点, 特定拠点准教授 (90410737)
• Co-Investigator(Kenkyū-buntansha): 梅山 有和 京都大学, 大学院工学研究科 分子工学専攻, 准教授 (30378806)
• Co-Investigator(Renkei-kenkyūsha): 田中 元雅 独立行政法人 理化学研究所, 田中研究ユニット, リーダー (40321781)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2012: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: ナノバイオサイエンス / 細胞工学 / 光治療

Outline of Final Research Achievements

Recent rapid progress in nanotechnology has enabled development of a wide variety of photo-responsive nanomaterials. Some of them have the ability to generate heat or reactive oxygen species under illumination, which can be utilized for medical and cell biological applications. However, under physiological conditions, nanomaterials are often colloidally unstable and cytotoxic. Thus, making their surface biocompatible is essential. In this study, the applicant aimed at exploration of photo-responsiveness of carbon nanotubes and of surface chemistry for gold nanoparticles using biomaterials. As a result, it was found that (1) a semiconducting component of carbon nanotubes is able to generate reactive oxygen species very efficiently even under near-infrared light that is the least invasive to our body and (2) genetically engineered serum protein-coated gold nanoparticles is able to warm the plasma membrane of heat-sensing neurons in a site-specific manner to safely activate them.

Research Products

• [Journal Article] Cytotoxicity of pure nanodrugs of SN-38 and podophyllotoxin dimers in human cancer HepG2, KPL-4 and MCF-7 cellsc (2015)
  • Author(s): Y. Koseki, Y. Ikuta, T. Murakami, T. Onodera, H. Oikawa, L. Cong, H. Tada, K. Gonda, N. Ohuchi, H. Kasai
  • Journal Title: Mol. Cryst. Liq. Cryst. Volume: 622 Issue: 1 Pages: 1-5
  • DOI: 10.1080/15421406.2015.1096483
  • Peer Reviewed
• [Journal Article] Thermosensitive Ion Channel Activation in Single Neuronal Cells by Using Surface-Engineered Plasmonic Nanoparticles. (2015)
  • Author(s): Nakatsuji H, Numata T, Morone N, Kaneko S, Mori Y, Imahori H, Murakami T.
  • Journal Title: Angewandte Chemie International Edition Volume: 54 Issue: 40 Pages: 11725-1729
  • DOI: 10.1002/anie.201505534
  • NAID: 120005646471
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Structural and functional changes in high-density lipoprotein induced by chemical modification (2015)
  • Author(s): T. Murakami, H. Okamoto, H. Kim
  • Journal Title: Biomater. Sci. Volume: 3 Issue: 5 Pages: 712-715
  • DOI: 10.1039/c4bm00402g
  • Peer Reviewed / Open Access
• [Journal Article] Internalization of high-density lipoproteins bearing arginine-rich peptides (2015)
  • Author(s): T. Murakami, H. Okamoto, H. Kim.
  • Journal Title: Chem. Lett. Volume: 44 Issue: 3 Pages: 336-338
  • DOI: 10.1246/cl.140989
  • NAID: 130004868368
  • Peer Reviewed
• [Journal Article] Control of the photoluminescence properties of single-walled carbon nanotubes by alkylation and subsequent thermal treatment (2015)
  • Author(s): Y. Maeda, Y. Takehara, M. Yamada, M. Suzuki, T. Murakami
  • Journal Title: Chem. Commun. Volume: 51 Issue: 70 Pages: 13462-13465
  • DOI: 10.1039/c5cc04020e
  • Peer Reviewed
• [Journal Article] Journal of Controlled Release (2014)
  • Author(s): Hashida, Y., Tanaka, H., Zhou, S., Kawakami, S., Yamashita, F., Murakami, T., Umeyama, T., Imahori, H., Hashida, M.
  • Journal Title: Photo thermal ablation of tumor cells using a single-walled carbon nanotube-peptide composite Volume: 173 Pages: 59-66
  • DOI: 10.1016/j.jconrel.2013.10.039
  • Peer Reviewed
• [Journal Article] Preparation of immunostiumulatory single-walled carbon nanotube/CpG DNA complexes and evaluation of their potential in cancer immunotherapy (2014)
  • Author(s): Zhou, S., Hashida, Y., Kawakami, S., Mihara, J., Umeyama, T., Imahori, H., Murakami, T. Yamashita, F. Hashida, M.
  • Journal Title: International Journal of Pharmaceutics Volume: 471 Issue: 1-2 Pages: 214-223
  • DOI: 10.1016/j.ijpharm.2014.05.037
  • Peer Reviewed
• [Journal Article] Mesoscopic Metal Nanoparticles Doubly Functionalized with natural and engineered lipidic dispersants for therapeutics (2014)
  • Author(s): Murakami, T., Nakatsuji, H., Morone, N., Heuser, J. E., Ishidate, F., Hashida, M., Imahori, H.
  • Journal Title: ACS Nano Volume: 8 Issue: 7 Pages: 7370-7376
  • DOI: 10.1021/nn5024818
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Photothermal ablation of tumor cells using a single-walled carbon nanotube-peptide composite (2014)
  • Author(s): Hashida, Y.; Tanaka, H.; Zhou, S.; Kawakami, S.; Ymashita, F.; Murakami, T.; Umeyama, T.; Imahori, H.: Hashida, M.
  • Journal Title: Journal of Controlled Release Volume: 173 Pages: 59-66
  • DOI: 10.1016/j.jconrel.2013.12.023
  • NAID: 120005474483
  • Peer Reviewed
• [Journal Article] Exclusive Photothermal Heat Generation by a Gadolinium Bis(naphthalocyanine) Complex and Inclusion into Modified High-Density Lipoprotein Nanocarriers for Therapeutic Applications (2013)
  • Author(s): Mathew S, Murakami T, Nakatsuji H, Okamoto H, Morone N, Heuser JE, Hashida M, Imahori H.
  • Journal Title: ACS Nano. Volume: 7(10) Issue: 10 Pages: 8908-16
  • DOI: 10.1021/nn403384k
  • Peer Reviewed
• [Journal Article] Fabrication of Pure Nanodrugs of Podophyllotoxin Dimer and Their Anticancer Activity (2013)
  • Author(s): Y. Ikuta, Y. Koseki, T. Murakami, M. Ueda, H. Oikawa, H. Kasai
  • Journal Title: Chem. Lett. Volume: 48 Issue: 8 Pages: 900-901
  • DOI: 10.1246/cl.130224
  • NAID: 10031189289
  • Peer Reviewed
• [Journal Article] Helicity Selective Photoreaction of Single-walled Carbon Nanotubes with Organosulfur Compounds in the Presence of Oxygen (2013)
  • Author(s): Maeda, Y.; Higo, J.; Amagai, Y.; Matsui, J.; Ohkubo, K.; Yoshigoe, Y.; Hashimoto, M.; Eguchi, K.; Yamada, M.; Hasegawa, T.; Sato, Y.; Zhou, J.; Lu, J.; Miyashita, T.; Fukuzumi, S.; Murakami, T.; Tohji, K.; Nagase, S; Akasaka, T.
  • Journal Title: J. Am. Chem. Soc. Volume: 135 Issue: 16 Pages: 6356-6362
  • DOI: 10.1021/ja402199n
  • Peer Reviewed
• [Journal Article] Caboxylated SiO2-coated alpha-Fe nanoparticles: towards a versatile platform for biomedical applications (2013)
  • Author(s): Kohara, K.; Yamamoto, S.; Seinberg, L.; Murakami, T.; Tsujimoto, M.; Ogawa, T.; Kurata, H.; Kageyama, H.; Takano, M.
  • Journal Title: Chemical Communications Volume: 49 Issue: 25 Pages: 2563-2565
  • DOI: 10.1039/c3cc39055a
  • Peer Reviewed
• [Journal Article] Photodynamic and photothermal effecrts of semiconducting and metallic-enriched single-walled carbon nanotubes (2012)
  • Author(s): Murakami, T., Nakatsuji, H., Inada, M., Matoba, Y., Umeyama, T., Tsujimoto, M. , Isoda, S., Hashida, M., Imahori, H.
  • Journal Title: Journal of the American Chemical Society Volume: 134 Issue: 43 Pages: 17862-17865
  • DOI: 10.1021/ja3079972
  • Peer Reviewed
• [Journal Article] Phospholipid nanodisc engineering for drug delivery systems (2012)
  • Author(s): Murakami, T.
  • Journal Title: Biotechnology Journal Volume: 7 Issue: 6 Pages: 762-767
  • DOI: 10.1002/biot.201100508
  • Peer Reviewed
• [Journal Article] Creation of pure nanodrugs and their anticancer properties (2012)
  • Author(s): H. Kasai, T. Murakami, Y. Ikuta, Y. Koseki, K. Baba, H. Oikawa, H. Nakanishi, M. Okada, M. Shoji, M. Ueda, H. Imahori, M. Hashida
  • Journal Title: Angew. Chem. Int. Ed Volume: 51 Issue: 41 Pages: 10315-10318
  • DOI: 10.1002/anie.201204596
  • Peer Reviewed
• [Journal Article] Utilization of Photo induced Charge-Separated State of Donor-Acceptor Linked Molecules for Regulation of Cell Membrane Potential and Ion Transport (2012)
  • Author(s): Numata T, Murakami T, Kawashima F, Morone N, Heuser JE, Takano Y, Ohkubo K, Fukuzumi S, Mori Y, Imahori H
  • Journal Title: J Am Chem Soc Volume: 134 Issue: 14 Pages: 6092-6095
  • DOI: 10.1021/ja3007275
  • Peer Reviewed
• [Journal Article] Single-walled carbon nanohorns as drug carriers : adsorption of prednisolone and anti-inflammatory effects on arthritis (2011)
  • Author(s): Nakamura M., Tsuchida K., 他6名
  • Journal Title: Nanotechnology Volume: 22巻 Issue: 46 Pages: 465102-465102
  • DOI: 10.1088/0957-4484/22/46/465102
  • Peer Reviewed
• [Presentation] Photoactivation of Thermosensitive Ion Channel with Surface Engineered Plasmonic Nanoparticle (2015)
  • Author(s): Hirotaka Nakatsuji, Tomohiro Numata, Nobuhiro Morone, Shuji Kaneko, Yasuo Mori, Hiroshi Imahori, and Tatsuya Murakami
  • Organizer: iCeMS International Symposium “Hierarchical Dynamics in Soft Materials and Biological Matter”
  • Place of Presentation: 京都大学 吉田北部キャンパス（京都府京都市）
  • Year and Date: 2015-08-25
  • Int'l Joint Research
• [Presentation] リポ蛋白質のナノバイオエンジニアリング (2015)
  • Author(s): 村上 達也、金 亨振、岡本 陽己
  • Organizer: 日本バイオマテリアル学会 第10回関西若手研究発表会
  • Place of Presentation: 関西大学 千里山キャンパス（大阪府吹田市）
  • Year and Date: 2015-08-05
• [Presentation] Development of pH-Dependent Endosomolytic High-Density Lipoprotein Nanoparticles (2015)
  • Author(s): Hyungjin Kim, Haruki Okamoto, Arnaud E. Felber, Anna Polomska, Nobuhiro Morone, John E. Heuser, Jean-Christophe Leroux, and Tatsuya Murakami
  • Organizer: 2015 CRS Annual Meeting & Exposition
  • Place of Presentation: Edinburgh, UK
  • Year and Date: 2015-07-28
  • Int'l Joint Research
• [Presentation] 脂質膜と膜混合する変異型高比重リポ蛋白質 (2015)
  • Author(s): 金 亨振、村上 達也
  • Organizer: 第31回日本DDS学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-07-03
• [Presentation] 遺伝子改変・化学修飾によるリポ蛋白質の機能変換 (2015)
  • Author(s): 村上 達也、岡本 陽己、金 亨振
  • Organizer: 第31回日本DDS学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-07-03
• [Presentation] Development of Endosomolytic Polyanion-Coated High-Density Lipoprotein Nanoparticles for Cytosolic Drug Delivery (2015)
  • Author(s): Hyungjin Kim, Haruki Okamoto, Arnaud E. Felber, Anna Polomska, Nobuhiro Morone, John E. Heuser, Jean-Christophe Leroux, and Tatsuya Murakami
  • Organizer: 第31回日本DDS学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-07-02
• [Presentation] 光熱変換ナノ材料の安全な細胞膜デリバリーと痛み受容体TRPV1の光制御 (2015)
  • Author(s): 中辻 博貴、沼田 朋大、諸根 信弘、John E. Heuser、高野 勇太、森 泰生、今堀 博、村上 達也
  • Organizer: 第31回日本DDS学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-07-02
• [Presentation] 単層カーボンナノチューブの光線力学効果のカイラリティ濃縮による増強 (2015)
  • Author(s): 福田亮介、中辻博貴、梅山有和、今堀博、村上達也
  • Organizer: 日本化学会第95回春季年会
  • Place of Presentation: 日本大学舟橋キャンパス
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 光熱変換ナノ材料の細胞膜精密配置による痛み受容体TRPV1の光制御 (2014)
  • Author(s): 中辻博貴、沼田朋大、高野勇太、森泰生、今堀博、村上達也
  • Organizer: 第36回日本バイオマテリアル学会大会
  • Place of Presentation: タワーホール船堀
  • Year and Date: 2014-11-17 – 2014-11-18
• [Presentation] 半導体性および金属性単層カーボンナノチューブの近赤外光応答性とその殺細胞活性 (2014)
  • Author(s): 村上達也
  • Organizer: 第1回ナノカーボンバイオシンポジウム
  • Place of Presentation: 名古屋大学
  • Year and Date: 2014-09-02
• [Presentation] カーボンナノチューブの光線力学効果 (2014)
  • Author(s): 村上達也、稲田真実、中辻博貴、梅山有和、今堀博
  • Organizer: 第30回日本DDS学会学術集会
  • Place of Presentation: 慶應義塾大学薬学部共立芝キャンパス
  • Year and Date: 2014-07-30 – 2014-07-31
  • Invited
• [Presentation] 細胞接着性金ナノロッドの作製と 細胞膜蛋白質の光制御への応用 (2014)
  • Author(s): 中辻博貴
  • Organizer: 日本化学会第94回春季年会
  • Place of Presentation: 名古屋大学
• [Presentation] 細胞膜透過性高比重リポタンパク質による金ナノロッドの生体適合化と細胞内送達 (2013)
  • Author(s): 中辻博貴
  • Organizer: 第93回日本化学会春季年会
  • Place of Presentation: 大津
  • Year and Date: 2013-03-23
• [Presentation] 近赤外光照射時に活性酸素種を高効率生成する単層カーボンナノチューブの探索と応用 (2013)
  • Author(s): 稲田真実
  • Organizer: 第93回日本化学会春季年会
  • Place of Presentation: 大津
  • Year and Date: 2013-03-23
• [Presentation] Light-harvesting carbon nanomaterials for cell biology and therapy (2013)
  • Author(s): Tatsuya Murakami
  • Organizer: RSC-iCeMS International Symposium
  • Place of Presentation: Kyoto(招待講演)
  • Year and Date: 2013-03-18
• [Presentation] Functionalization and biomedical applications of naturally-occurring nanodisc (2013)
  • Author(s): Tatsuya Murakami
  • Organizer: The 7th Annual Meeting of the Nano Biomedical Society
  • Place of Presentation: Kyoto(招待講演)
  • Year and Date: 2013-01-24
• [Presentation] ナノテクノロジーを用いた難病治療法の開発に向けて (2013)
  • Author(s): 村上達也
  • Organizer: 福井プロジェクト・グループ主催 岡山大学・岡山理科大学・津山工専Tryアングル・インターネット講演会
  • Place of Presentation: 津山工専
  • Invited
• [Presentation] 光応答性ナノ材料による細胞工学と難病治療 (2013)
  • Author(s): 村上達也
  • Organizer: 第10回光科学若手研究会
  • Place of Presentation: 京都大学宇治キャンパス
  • Invited
• [Presentation] カーボンナノチューブの光線力学効果と殺細胞活性 (2013)
  • Author(s): 村上達也
  • Organizer: 第29回日本DDS学会学術集会
  • Place of Presentation: 京都テルサ
• [Presentation] サンドイッチ型ナフタロシアニン錯体内包リポ蛋白質の光照射による熱選択的産生と殺細胞活性 (2013)
  • Author(s): 村上達也
  • Organizer: 第35回日本バイオマテリアル学会大会
  • Place of Presentation: タワーホール船堀
• [Presentation] カチオン性ペプチド融合高比重リポタンパク質の開発 (2013)
  • Author(s): Hyungjin Kim
  • Organizer: 第35回日本バイオマテリアル学会大会
  • Place of Presentation: タワーホール船堀
• [Presentation] Enhancement of Photodynamic Effect by Single Chirality Separation of Semiconducting Single-walled Carbon Nanotubes: Application to Photodynamic Therapy (2013)
  • Author(s): 村上達也
  • Organizer: CBI学会2013年大会
  • Place of Presentation: タワーホール船堀
• [Presentation] ディスク状高比重リポタンパク質と金ナノロッドの融合 : 新しい有機無機複合材料の作製と機能評価 (2012)
  • Author(s): 中辻博貴
  • Organizer: 第34回日本バイオマテリアル学会
  • Place of Presentation: 仙台
  • Year and Date: 2012-11-27
• [Presentation] 近赤外光照射時に活性酸素種を高効率生成する単層カーボンナノチューブの探索 : 光線力学的療法への応用を目指して (2012)
  • Author(s): 稲田真実
  • Organizer: 第34回日本バイオマテリアル学会
  • Place of Presentation: 仙台
  • Year and Date: 2012-11-26
• [Presentation] Biochemical engineering of mesosocale lipid-protein composite biomaterials for drug delivery system (2012)
  • Author(s): Tatsuya Murakami
  • Organizer: Crossing Boundaries : Stem Cells, Materials, Mesoscopic Sciences, and Beyond
  • Place of Presentation: Beijing(china)(招待講演)
  • Year and Date: 2012-09-21
• [Presentation] Discoidal HDL engineering for drug delivery systems : size control by drug loading and intracellular delivery of drug (2012)
  • Author(s): Tatsuya Murakami
  • Organizer: 80th European Atherosclerosis Society Congress
  • Place of Presentation: Milan(Italy)
• [Presentation] Photothermal and photodynamic effects of metallic- and semiconducting-enriched single walled carbon nanotubes (2012)
  • Author(s): Tatsuya Murakami
  • Organizer: 6th Annual Symposium on Nanobiotechnology ″Kyoto Cell-Material Integration 2012″
  • Place of Presentation: Kyoto
• [Remarks] 光を使って神経細胞の「痛み」感知を制御する手法を開発：新しい鎮痛療法の可能性
  • URL: http://www.icems.kyoto-u.ac.jp/j/pr/2015/08/06-nr.html
• [Remarks] 京都大学iCeMS村上達也グループ
  • URL: http://www.murakami.icems.kyoto-u.ac.jp
• [Remarks] iCeMS村上グループ
  • URL: http://www.murakami.icems.kyoto-u.ac.jp/
• [Remarks] 京都大学iCeMS村上グループホームページ
  • URL: http://www.murakami.icems.kyoto-u.ac.jp/