Nagase, Kenichi

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmaceutical Sciences 創薬分析化学講座 (Shiba-Kyoritsu)

Position

Associate Professor

Profile Summary 【 Display / hide

Career 【 Display / hide

  • 2005.04
    -
    2007.03

    Tokyo Women's Medical University, Institute of Advanced Biomedical Engineering and Science, Postdoctoral Research Fellow

  • 2007.04
    -
    2011.03

    Tokyo Women's Medical University, Institute of Advanced Biomedical Engineering and Science, Assistant Professor

  • 2011.04
    -
    2017.03

    Tokyo Women's Medical University, Institute of Advanced Biomedical Engineering and Science, Lecturer

Academic Background 【 Display / hide

  • 1996.04
    -
    2000.03

    Waseda University, School of Science and Engineering, Department of Chemical Engineering

    Japan, University, Graduated

  • 2000.04
    -
    2002.03

    Waseda University, Graduate School of Science and Engineering, Department of Chemical Engineering

    Japan, Graduate School, Completed, Master's course

  • 2002.04
    -
    2005.03

    Waseda University, Graduate School of Science and Engineering, Department of Chemical Engineering

    Japan, Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(工学), Waseda University, Coursework, 2005.03

Licenses and Qualifications 【 Display / hide

  • 日本分析化学会 液体クロマトグラフィー分析士 初段, 2017.09

 

Books 【 Display / hide

  • 生体内移動論

    長瀬 健一, 朝倉書店, 2021.08

    Scope: 第8章 薬物移動論,  Contact page: 362-408

  • Stimuli-Responsive Polymers Handbook

    Kenichi Nagase, Hideko Kanazawa, 株式会社エヌ・ティー・エス, 2018.12

    Scope: 温度応答性クロマトグラフィー

  • Temperature‐responsive Polymers for Tissue Engineering

    Kenichi Nagase, Masayuki Yamato, Teruo Okano, John Wiley & Sons, 2018.06

    Scope: Temperature‐Responsive Polymers: Chemistry, Properties and Applications

  • Polymer and Biopolymer Brushes: For Materials Science and Biotechnology

    Kenichi Nagase, Teruo Okano, John Wiley & Sons, 2018.01

    Scope: Thermoresponsive Polymer Brushes for Thermally Modulated Cell Adhesion and Detachment

  • バイオマテリアル-その基礎と先端研究への応用

    Kenichi Nagase、Masayuki Yamato, 東京化学同人, 2016.02

    Scope: 細胞シート

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Papers 【 Display / hide

  • Viral vector purification with thermoresponsive-anionic mixed polymer brush modified beads-packed column

    Nagase, Kenichi, Kitazawa, Sakiko, Kogure, Toshihiko, Yamada, Sota, Katayama, Kazuhiro and Kanazawa, Hideko

    Separation and Purification Technology (Elsevier)  286   120445 2022.04

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1383-5866

     View Summary

    Viral vectors have attracted attention as a potential new therapeutic modality for gene therapy. In this study, we developed a temperature-modulated viral vector purification column using a mixed polymer brush composed of thermoresponsive and anionic polymers as packing material ligands. The mixed polymer brushes were modified on silica beads using a combination of reversible addition − fragmentation chain transfer (RAFT) polymerization of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and subsequent atom transfer radical polymerization (ATRP) of N-isopropylacrylamide (NIPAAm). The temperature-modulated zeta potential change in the prepared mixed polymer brush was attributed to the PNIPAAm shrinking and exposing of PAMPS. The prepared mixed polymer brush modified beads were used as packing materials, and the elution behavior of the adeno associated virus type 2 (AAV2) vector was observed. The AAV2 vector was adsorbed on the mixed polymer brush by electrostatic and hydrophobic interactions at 40 °C. By reducing the temperature to 5 °C, adsorbed AAV2 vector on the mixed polymer brush was desorbed and eluted from the column due to lowering the electrostatic and hydrophobic interactions between the AAV2 vector and mixed polymer brush. The AAV2 vector was separated from bovine serum proteins as a contaminant using the column. The ability to infect cells was maintained by the recovered AAV2 vectors from the column. Thus, the developed column would be beneficial for the simple purification of viral vectors.

  • Temperature responsive chromatography for therapeutic drug monitoring with an aqueous mobile phase

    Kenichi Nagase, Teruno Nishiyama, Masakazu Inoue, Hideko Kanazawa

    Scientific Reports (Nature Publishing Group)  11 ( 1 ) 23508 2021.12

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2045-2322

     View Summary

    Therapeutic drug monitoring is a key technology for effective pharmacological treatment. In the present study, a temperature-responsive chromatography column was developed for safe and simple therapeutic drug monitoring without the use of organic solvents. Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel-modified silica beads were prepared via a condensation reaction and radical polymerization. The temperature-dependent elution behavior of the drugs was observed using a PNIPAAm-modified silica-bead packed column and an all-aqueous mobile phase. Sharp peaks with reproducible retention times were observed at temperatures of 30 °C or 40 °C because the PNIPAAm hydrogel on the silica beads shrinks at these temperatures, limiting drug diffusion into the PNIPAAm hydrogel layer. The elution behavior of the sample from the prepared column was examined using a mixture of serum and model drugs. The serum and drugs were separated on the column at 30 °C or 40 °C, and the concentration of the eluted drug was obtained using the calibration curve. The results show that the prepared chromatography column would be useful for therapeutic drug monitoring because the drug concentration in serum can be measured without using organic solvents in the mobile phase and without any need for sample preparation.

  • Thermally-modulated cell separation columns using a thermoresponsive block copolymer brush as a packing material for the purification of mesenchymal stem cells

    Kenichi Nagase, Goro Edatsune, Yuki Nagata, Junnosuke Matsuda, Daiju Ichikawa, Sota Yamada, Yutaka Hattori, Hideko Kanazawa

    Biomaterials Science (The Royal Society of Chemistry)  9 ( 21 ) 7054 - 7064 2021.10

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2047-4830

     View Summary

    Cell therapy using mesenchymal stem cells (MSCs) is used as effective regenerative treatment. Cell therapy requires effective cell separation without cell modification and cellular activity reduction. In this study, we developed a temperature-modulated mesenchymal stem cell separation column. A temperature-responsive cationic block copolymer, poly(N,N-dimethylaminopropylacrylamide)-b-poly(N-isopropylacrylamide)(PDMAPAAm-b-PNIPAAm) brush with various cationic copolymer compositions, was grafted onto silica beads via two-step atom transfer radical polymerization. Using the packed beads, the elution behavior of the MSCs was observed. At 37 °C, the MSCs were adsorbed onto the column via both hydrophobic and electrostatic interactions with the PNIPAAm and PDMAPAAm segments of the copolymer brush, respectively. By reducing the temperature to 4 °C, the adsorbed MSCs were eluted from the column by reducing the hydrophobic and electrostatic interactions attributed to the hydration and extension of the PNIPAAm segment of the block copolymer brush. From the temperature-modulated adsorption and elution behavior of MSCs, a suitable DMAPAAm composition of the block copolymer brush was determined. Using the column, a mixture of MSC and BM-CD34+ cells was separated by simply changing the column temperature. The column was used to purify the MSCs, with purities of 78.2%, via a temperature change from 37 °C to 4 °C. Additionally, the cellular activity of the MSCs was retained throughout the column separation step. Overall, the obtained results show that the developed column is useful for MSC separation without cell modification and cellular activity reduction.

  • Temperature-responsive spin column for sample preparation using an all-aqueous eluent

    Nagase, Kenichi, Ishizawa, Yuta, Inoue, Masakazu, Kokubun, Matsurika, Yamada, Sota and Kanazawa, Hideko

    Analytica Chimica Acta 1179   338806 2021.09

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0003-2670

     View Summary

    We present a temperature-responsive spin column using an all-aqueous eluent. The method is intended as a simple sample preparation method for protein removal from serum, which is required for serum drug analysis. As packing materials for the spin column, we prepared two types of silica beads via surface-initiated radical polymerization. The large beads (diameter, 40–63 μm) were grafted with a temperature-responsive cationic copolymer, poly(N-isopropylacrylamide-co-N,N-dimethylaminopropyl acrylamide-co-n-butyl methacrylate) (P(NIPAAm-co-DMAPAAm-co-BMA)), and the small beads (diameter, 5 μm) were grafted with a temperature-responsive hydrophobic copolymer, P(NIPAAm-co-BMA). The beads were packed into the spin column as a double layer: P(NIPAAm-co-BMA) silica beads on the bottom and P(NIPAAm-co-DMAPAAm-co-BMA) silica beads on the top. The sample purification efficacy of the prepared spin column was evaluated on a model sample analyte (the antifungal drug voriconazole mixed with blood serum proteins). At 40 °C, the serum proteins and voriconazole were adsorbed on the prepared spin column via hydrophobic and electrostatic interactions. When the temperature was decreased to 4 °C, the adsorbed voriconazole was eluted from the column with the pure water eluent, while the serum proteins remained in the column. This temperature-responsive spin column realizes sample preparation simply by changing the temperature.

  • Anion species-triggered antibody separation system utilizing a thermo-responsive polymer column under optimized constant temperature

    Nomoto, Daiki, Nagase, Kenichi, Nakamura, Yubuki, Kanazawa, Hideko, Citterio, Daniel and Hiruta, Yuki

    Colloids and Surfaces B: Biointerfaces 205   111890 2021.09

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0927-7765

     View Summary

    Although the field of antibody drugs has grown larger, the antibody production still faces several challenges. Effective antibody purification is required, but the conventional purification method for antibodies is cost intensive and often causes aggregation problems, indicating the need for new alternative antibody purification methods. In the present study, a constant temperature antibody purification system for use with a thermo-responsive polymer column was developed based on switching of anion species in eluents. By adjusting the temperature for each antibody, the developed column enabled separation of the therapeutic monoclonal antibodies, rituximab and trastuzumab, from contaminants without changing salt concentration or pH of the eluents. The thermo-responsive hydrogel-modified column packing material was synthesized by introducing n-butyl methacrylate, acrylic acid, N,N′-methylenebisacrylamide and N-isopropylacrylamide to the surface of silica beads with an initiator by a graft-from approach. Elution behavior of antibodies with three types of anions, such as citrate, phosphate, and chloride were tested under three different temperature conditions. It was demonstrated that the thermo-responsive hydrogel grafted column showed a switchable antibody retention behavior at constant temperature and salt concentration, with antibody adsorption by NaCl eluent and desorption by citric acid buffer eluent.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • 温度応答性高分子を利用した抗体医薬品分離技術の開発

    長瀬 健一,金澤 秀子

    B&I バイオサイエンスとインダストリー 79 ( 1 ) 38 - 39 2021.01

    Introduction and explanation (scientific journal), Joint Work,  ISSN  09148981

  • 刺激応答性高分子を用いたバイオセパレーション

    長瀬 健一,金澤 秀子

    高分子 69 ( 9 ) 472 - 473 2020.09

    Introduction and explanation (scientific journal), Joint Work

  • 効果的な心筋細胞シート移植のためのVEGF徐放ファイバーマットの開発

    長瀬健一, 金澤秀子

    Drug Delivery System (じほう)  34 ( 3 ) 173 - 178 2019.07

    Introduction and explanation (scientific journal), Joint Work,  ISSN  0913-5006

  • 微細構造表面と温度応答性高分子を用いた細胞分離技術の開発

    長瀬, 健一, 宿輪, 理紗, 小沼, 隆大, 大和, 雅之, 武田, 直哉 and 岡野, 光夫

    バイオマテリアル -生体材料- 36 ( 2 ) 158 - 159 2018.04

    Introduction and explanation (scientific journal), Joint Work

  • 積層化細胞シートの移植効率向上を目的とした細胞増殖因子徐放ファイバーマットの開発

    長瀬, 健一, 関根, 秀一, 清水, 達也, 金澤, 秀子, 岡野, 光夫, Lee, Seung Jin and 大和, 雅之

    Bioindustry (CMC出版)  35 ( 4 ) 36 - 45 2018.04

    Introduction and explanation (scientific journal), Joint Work

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Presentations 【 Display / hide

  • Temperature responsive mixed mode chromatography for effective separation of ionic biomolecules

    Kenichi Nagase, Sakiko Kitazawa, Maria Watanabe, Fumihiko Zen, Sota Yamada, Hideko Kanazawa

    The International Chemical Congress of Pacific Basin Societies 2021 (PacifiChem2021), 2021.12, Oral Presentation(general)

  • Temperature-modulated cell separation column using thermoresponsive cationic copolymer modified beads

    Kenichi Nagase, Daimu Inanaga, Aya Mizutani Akimoto, Hideko Kanazawa

    The International Chemical Congress of Pacific Basin Societies 2021 (PacifiChem2021), 2021.12, Poster (general)

  • Thermoresponsive ionic copolymer brushes for temperature modulated cell separations

    Kenichi Nagase, Naho Uchikawa, Ayumu Ohta, Tadashi Hirotani, Aya Mizutani Akimoto, Hideko Kanazawa

    The International Chemical Congress of Pacific Basin Societies 2021 (PacifiChem2021), 2021.12, Poster (general)

  • Cell Separation Column using Thermoresponsive Block Copolymer Brush Modified Silica Bead as Packing Materials

    Kenichi Nagase, Goro Edatsune, Hideko Kanazawa

    8th Asian Biomaterials Congress, (8th ABMC), 2021.11, Poster (general)

  • 細胞認識ペプチドを用いた温度制御型細胞分離法の開発

    長瀬健一, 志村昌紀, 島根瑠霞, 金澤 秀子

    第43回日本バイオマテリアル学会大会, 2021.11, Poster (general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 生体分子・細胞との相互作用を制御する革新的水圏機能材料の創製

    2020.04
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    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 長瀬 健一, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • 再生医療を革新的に効率化する機能性バイオ界面の創製

    2019.04
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    2023.03

    MEXT, JSPS, 長瀬健一, 基盤研究(B) , Principal Investigator

  • 酸素産生ナノ粒子を用いた革新的細胞組織移植法の確立

    2018.06
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    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 長瀬 健一, Grant-in-Aid for Challenging Research (Exploratory) , Principal Investigator

  • mRNA送達による立体細胞組織内タンパク質発現を利用した脈管形成と血管新生誘導

    2018.04
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    2022.03

    MEXT, JSPS, Grant-in-Aid for Scientific Research, 小林 純, Co-investigator

  • Development of Intelligent Cell Separation Materials with Cell Recognition

    2014.04
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    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 長瀬 健一, Grant-in-Aid for Scientific Research (C), Principal Investigator

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Awards 【 Display / hide

  • SCS32 Best Presentation Award

    2021.11

    Type of Award: Awards of National Conference, Council and Symposium

  • 高分子学会 広報委員会パブリシティ賞

    長瀬健一, 2021.08, 公益社団法人 高分子学会, 温度応答性-カチオン性ブロック共重合体による幹細胞分離法の開発

    Type of Award: Awards of National Conference, Council and Symposium.  Country: 日本

  • 第5回バイオインダストリー奨励賞

    長瀬健一, 2021.07, 一般財団法人バイオインダストリー協会, 機能性界面を用いたバイオ医薬品・治療用細胞 の革新的分離精製法の開発

    Type of Award: Other Awards.  Country: 日本

  • 学部長賞 研究部門

    2020

    Type of Award: Keio commendation etc.

  • 日本分析化学会 関東支部 新世紀賞

    2019.01

    Country: 日本

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Courses Taught 【 Display / hide

  • STUDY OF MAJOR FIELD (ANALYTICAL CHEMISTRY FOR DRUG DISCOVERY)

    2021

  • SEMINAR (ANALYTICAL CHEMISTRY FOR DRUG DISCOVERY)

    2021

  • RESEARCH FOR BACHELOR'S THESIS 1

    2021

  • PHYSICAL CHEMISTRY 3

    2021

  • PHYSICAL CHEMISTRY 1

    2021

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