生体共焦点・多光子イメージングによる内耳聴覚生理と病態生理の解明

2015 Fiscal Year Annual Research Report

• Project/Area Number: 26670738
• Research Institution: The University of Tokyo
• Principal Investigator: 松本 有 東京大学, 医学部附属病院, 助教 (80548553)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 耳科学 / 生体イメージング

Outline of Annual Research Achievements

初年度の報告で解決出来なかった「蛍光カルシウムインジケーターのloading条件」について引き続き検討した。FLUO-4AMよりはOregon Green 488 BAPTA-1 AMの方がS/N比が改善した。他の試薬は大差なかった。また体動の抑制についてもさらに検討を行った。モルモットはマウスに比べて大型なので呼吸によるブレも大きい。頭部をさらにしっかりと固定できるような金具を考案した。気管切開をして人工呼吸器に繋ぐと、撮影時間だけ呼吸を止めておくことが出来る。蝸牛頂回転を開窓しOregon Green 488 BAPTA-1 AMを用いてloadingした。外耳道に挿入したイヤホンから音響刺激を行い、Nikon A1R高速共焦点顕微鏡を用いて撮影した。外有毛細胞にROIを設定し、蛍光強度の経時的変化を解析した。音響刺激に一致して外有毛細胞のカルシウム濃度上昇を捉えることに成功した。また活性酸素検出用蛍光試薬であるAminophenyl Fluorescein (APF)およびHydroxyphenyl Fluorescein (HPF)を用い、ミトコンドリア電子伝達系酵素阻害剤であるアンチマイシンAの直接滴下によりラセン神経節近傍の活性酸素産生を直接検出することに成功した。引き続き再現性を確認するための実験や、最近発売となった新たな蛍光試薬の試用、刺激音の調整などを行っている。

Research Products

• [Journal Article] Systemically Injectable Enzyme-Loaded Polyion Complex Vesicles as in Vivo Nanoreactors Functioning in Tumors (2016)
  • Author(s): Anraku Y, Kishimura A, Kamiya M, Tanaka S, Nomoto T, Toh K, Matsumoto Y, Fukushima S, Sueyoshi D, Kano MR, Urano Y, Nishiyama N, Kataoka K
  • Journal Title: Angew Chem Int Ed Engl Volume: 55 Pages: 560-5
  • DOI: 10.1002/anie.201508339
  • Peer Reviewed
• [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
  • Journal Title: Cancer Science Volume: in press Pages: in press
  • DOI: 10.1111/cas.12926
  • Peer Reviewed
• [Journal Article] Vascular Bursts Enhance Permeability of Tumour Blood Vessels and Improve Nanoparticle Delivery (2016)
  • Author(s): Matsumoto Y, Nichols JW, Toh K, Nomoto T, Cabral H, Miura Y, Christie RJ, Yamada N, Ogura T, Kano MR, Matsumura Y, Nishiyama N, Yamasoba T, Bae YH, Kataoka K
  • Journal Title: Nat Nanotechnol Volume: in press Pages: in press
  • DOI: 10.1038/nnano.2015.342
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Systemic Delivery of Sirna by Actively Targeted Polyion Complex Micelles for Silencing the E6 and E7 Human Papillomavirus Oncogenes (2016)
  • Author(s): Nishida H, Matsumoto Y, Kawana K, Christie RJ, Naito M, Kim BS, Toh K, Min HS, Yi Y, Matsumoto Y, Kim HJ, Miyata K, Taguchi A, Tomio K, Yamashita A, Inoue T, Nakamura H, Fujimoto A, Sato M, Yoshida M, Adachi K, Arimoto T, Wada-Hiraike O, Oda K, Nagamatsu T, Nishiyama N, Kataoka K, Osuga Y, Fujii T
  • Journal Title: J Control Release Volume: in press Pages: in press
  • DOI: 10.1016/j.jconrel.2016.03.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Calcium Phosphate-Based Organic–Inorganic Hybrid Nanocarriers with Ph-Responsive on/Off Switch for Photodynamic Therapy (2016)
  • Author(s): Nomoto T, Fukushima S, Kumagai M, Miyazaki K, Inoue A, Mi P, Maeda Y, Toh K, Matsumoto Y, Morimoto Y, Kishimura A, Nishiyama N, Kataoka K
  • Journal Title: Biomater. Sci. Volume: in press Pages: in press
  • DOI: 10.1039/c6bm00011h
  • Peer Reviewed
• [Journal Article] Analyzing Spatiotemporal Distribution of Uniquely Fluorescent Nanoparticles in Xenograft Tumors (2016)
  • Author(s): Stirland DL, Matsumoto Y, Toh K, Kataoka K, Bae YH
  • Journal Title: J Control Release Volume: in press Pages: in press
  • DOI: 10.1016/j.jconrel.2016.02.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Design of High-Performance Anti-Adhesion Agent Using Injectable Gel with an Anti-Oxidative Stress Function (2015)
  • Author(s): Nakagawa H, Matsumoto Y, Matsumoto Y, Miwa Y, Nagasaki Y
  • Journal Title: Biomaterials Volume: 69 Pages: 165-73
  • DOI: 10.1016/j.biomaterials.2015.08.018
  • Peer Reviewed
• [Journal Article] Crgd-Installed Polymeric Micelles Loading Platinum Anticancer Drugs Enable Cooperative Treatment against Lymph Node Metastasis (2015)
  • Author(s): Makino J, Cabral H, Miura Y, Matsumoto Y, Wang M, Kinoh H, Mochida Y, Nishiyama N, Kataoka K
  • Journal Title: J Control Release Volume: 220 Pages: 783-91
  • DOI: 10.1016/j.jconrel.2015.10.017
  • Peer Reviewed
• [Journal Article] Ternary Polyplex Micelles with Peg Shells and Intermediate Barrier to Complexed DNA Cores for Efficient Systemic Gene Delivery (2015)
  • Author(s): Li J, Chen Q, Zha Z, Li H, Toh K, Dirisala A, Matsumoto Y, Osada K, Kataoka K, Ge Z
  • Journal Title: J Control Release Volume: 2015 Pages: 77-87
  • DOI: 10.1016/j.jconrel.2015.04.024
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Density-Tunable Conjugation of Cyclic Rgd Ligands with Polyion Complex Vesicles for the Neovascular Imaging of Orthotopic Glioblastomas (2015)
  • Author(s): Kawamura W, Miura Y, Kokuryo D, Toh K, Yamada N, Nomoto T, Matsumoto Y, Sueyoshi D, Liu X, Aoki I, Kano MR, Nishiyama N, Saga T, Kishimura A, Kataoka K
  • Journal Title: Science and Technology of Advanced Materials Volume: 16 Pages: 035004
  • DOI: 10.1088/1468-6996/16/3/035004
  • Peer Reviewed
• [Journal Article] Systemic Targeting of Lymph Node Metastasis through the Blood Vascular System by Using Size-Controlled Nanocarriers (2015)
  • Author(s): Cabral H, Makino J, Matsumoto Y, Mi P, Wu H, Nomoto T, Toh K, Yamada N, Higuchi Y, Konishi S, Kano MR, Nishihara H, Miura Y, Nishiyama N, Kataoka K
  • Journal Title: ACS Nano Volume: 9 Pages: 4957-67
  • DOI: 10.1021/nn5070259
  • Peer Reviewed
• [Presentation] Tips and Tricks in Transcanal Endoscopic Ear Surgery (2015)
  • Author(s): Matsumoto Y
  • Organizer: 13th Japan-Taiwan Conference on Otolaryngology-Head and Neck Surgery
  • Place of Presentation: Hitotsubashi Hall, National Center of Sciences, Tokyo, Japan
  • Year and Date: 2015-12-04
  • Int'l Joint Research / Invited
• [Presentation] Intravital Imaging of Drug Delivery Systems (2015)
  • Author(s): Matsumoto Y
  • Organizer: 2015 Conference on Developmental Biology Scientific & Drug Delivery System Program
  • Place of Presentation: Academia Sinica, Taipei, Taiwan
  • Year and Date: 2015-11-10
  • Int'l Joint Research / Invited
• [Presentation] 高齢者の人工聴覚器（人工中耳・人工内耳）の適応・実施上の留意点 (2015)
  • Author(s): 松本 有
  • Organizer: 第25回日本耳科学会総会・学術講演会
  • Place of Presentation: 長崎ブリックホール、長崎県長崎市
  • Year and Date: 2015-10-09
  • Invited
• [Presentation] Intravital Confocal / Two Photon Microscopy (2015)
  • Author(s): Matsumoto Y
  • Organizer: NIS 8th Nikon Microscope Image Forum
  • Place of Presentation: Haifeng International Hotel, Haidong City, Qinghai, China
  • Year and Date: 2015-07-28
  • Int'l Joint Research / Invited