Direct molecular delivery into nucleus by spatiotemporally controlled enhanced Mie scattering light

• Project/Area Number: 26560263
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical systems
• Research Institution: Keio University
• Principal Investigator: Terakawa Mitsuhiro 慶應義塾大学, 理工学部(矢上), 准教授 (60580090)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: フェムト秒レーザー / ドラッグデリバリー / レーザー医療 / 低侵襲治療システム

Outline of Final Research Achievements

High-throughput processing of cell nuclear membrane was investigated by using ultrafast enhanced Mie scattering light. Simultaneous laser ablation of cell membrane and nuclear membrane was also studied for achieving direct molecular delivery into nucleus. The fluorescence of the plasmid DNA/liposome complexes was detected in the nucleus as well as cytoplasm after laser illumination for microspheres. The direct delivery of complexes into the nucleus is probably attributed to the enhancement of the nuclear membrane permeability by the enhanced optical field obtained close to the nucleus.

Research Products

• [Int'l Joint Research] Laser Zentrum Hannover e.V./Leibniz University Hannover(ドイツ)
• [Journal Article] Intracellular localization and delivery of plasmid DNA by biodegradable microsphere-mediated femtosecond laser optoporation (2017)
  • Author(s): Atsuhiro Ishii, Yuki Hiruta, Dag Heinemann, Alexander Heisterkamp, Hideko Kanazawa, Mitsuhiro Terakawa
  • Journal Title: Journal of Biophotonics Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Biodegradable microsphere-mediated cell perforation using femtosecond laser (2016)
  • Author(s): Atsuhiro Ishii, Kazumasa Ariyasu, Tatsuki Mitsuhashi, Dag Heinemann, Alexander Heisterkamp, Mitsuhiro Terakawa
  • Journal Title: Journal of Biomedical Optics Volume: 21 Issue: 5 Pages: 055001-055001
  • DOI: 10.1117/1.jbo.21.5.055001
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] フェムト秒レーザーによる微粒子を用いた極微細加工と生体応用 (2016)
  • Author(s): 寺川 光洋, 石井 敦浩
  • Journal Title: レーザー研究 Volume: 44 Pages: 809-813
  • NAID: 130007957268
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Intracellular localization of plasmid-DNA on dielectric microsphere-mediated gene transfection using femtosecond laser (2017)
  • Author(s): Atsuhiro Ishii, Yuki Hiruta, Dag Heinemann, Alexander Heisterkamp, Hideko Kanazawa, Mitsuhiro Terakawa
  • Organizer: SPIE Photonics West 2017
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 2017-01-28
  • Int'l Joint Research
• [Presentation] 超短パルスレーザと生分解性ポリマーの相互作用およびドラッグデリバリーへの応用 (2016)
  • Author(s): 寺川光洋
  • Organizer: 第86回レーザ加工学会講演会
  • Place of Presentation: 岡山大学（岡山県・岡山市）
  • Year and Date: 2016-12-12
• [Presentation] Gene transfection using femtosecond laser-excited focused optical field with cationic liposome (2016)
  • Author(s): Atsuhiro Ishii, Yuki Hiruta, Yusuke Akutsu, Kazumasa Ariyasu, Shunichi Sato, H. Kanazawa, Mitsuhiro Terakawa
  • Organizer: European Materials Research Society (E-MRS) Spring Meeting 2016
  • Place of Presentation: Lille (France)
  • Year and Date: 2016-05-02
  • Int'l Joint Research
• [Presentation] マイクロ流路内における生分解性粒子支援フェムト秒レーザー外来分子導入 (2016)
  • Author(s): 石井敦浩、有安和優、三橋龍樹、Dag Heinemann、Alexander Heisterkamp、寺川光洋
  • Organizer: 第63回応用物理学会春季学術講演会
  • Place of Presentation: 東京工業大学大岡山キャンパス(東京都・目黒区)
  • Year and Date: 2016-03-19
• [Presentation] 生分解性粒子へのナノ秒パルスレーザー照射により発生する衝撃波の圧力算出 (2016)
  • Author(s): 鈴木皓大、阿久津佑介、矢田周平、小田貴大、安藤景太、寺川光洋
  • Organizer: 第16回レーザー学会東京支部研究会
  • Place of Presentation: 東海大学高輪キャンパス（東京都・港区）
  • Year and Date: 2016-03-05
• [Presentation] フェムト秒レーザー励起集光場によるプラスミドDNAの細胞内導入 (2016)
  • Author(s): 石井敦浩、蛭田勇樹、阿久津佑介、金沢秀子、寺川光洋
  • Organizer: レーザー学会学術講演会第36回年次大会
  • Place of Presentation: 名城大学天白キャンパス(愛知県・名古屋市天白区)
  • Year and Date: 2016-01-09
• [Presentation] Polymer microsphere-mediated cell membrane perforation using microfluidic channel (2015)
  • Author(s): Mitsuhiro Terakawa, Atsuhiro Ishii, Tatsuki Mitsuhashi,
  • Organizer: The 7th International Congress on Laser Advanced Materials Processing
  • Place of Presentation: 北九州国際会議場（福岡県・北九州市）
  • Year and Date: 2015-05-26
• [Presentation] Enhanced-ultrafast optical field for biomedical applications (2015)
  • Author(s): Mitsuhiro Terakawa, Kazumasa Ariyasu, Atsuhiro Ishii
  • Organizer: European Materials Research Society, Spring Meeging 2015
  • Place of Presentation: Lille（France）
  • Year and Date: 2015-05-11
  • Int'l Joint Research / Invited
• [Presentation] PLGA粒子を用いたフェムト秒レーザー励起集光場による外来分子導入 (2015)
  • Author(s): 石井敦浩、有安和優、寺川光洋
  • Organizer: 第15回レーザー学会東京支部研究会
  • Place of Presentation: 東海大学高輪キャンパス（東京都港区）
  • Year and Date: 2015-03-05
• [Presentation] 生分解性粒子へのナノ秒パルスレーザー照射により発生する衝撃波の観察 (2015)
  • Author(s): 鈴木皓大、阿久津佑介、 島田卓一郎、 矢田周平、 有安和優、 寺川光洋
  • Organizer: 第15回レーザー学会東京支部研究会
  • Place of Presentation: 東海大学高輪キャンパス（東京都港区）
  • Year and Date: 2015-03-05
• [Presentation] Femtosecond laser nanoprocessing toward drug delivery and tissue engineering (2014)
  • Author(s): Mitsuhiro Terakawa, Shuhei Yada, Kazumasa Ariyasu, Akimichi Shibata
  • Organizer: European Material Research Society (E-MRS) Fall Meeting 2014
  • Place of Presentation: ワルシャワ（ポーランド）
  • Year and Date: 2014-09-15 – 2014-09-18