Tsukada, Kosuke

写真a

Affiliation

Faculty of Science and Technology, Department of Applied Physics and Physico-Informatics (Yagami)

Position

Professor

Related Websites

External Links

Career 【 Display / hide

  • 2001.04
    -
    2002.03

    日本学術振興会特別研究員

  • 2002.04
    -
    2004.03

    川崎医科大学助手(生理学教室)

  • 2004.04
    -
    2009.03

    慶應義塾大学医学部助手(医化学教室)

  • 2007.04
    -
    2009.03

    マサチューセッツ総合病院,ハーバード大学医学部フェロー

Academic Degrees 【 Display / hide

  • 博士(工学), Keio University, 2002.03

  • 博士(医学), Keio University, 2013.03

 

Research Areas 【 Display / hide

  • Biomedical engineering/Biomaterial science and engineering

Research Keywords 【 Display / hide

  • 医用光工学

  • 微小循環学

  • 生体医工学

  • 腫瘍生物学

 

Papers 【 Display / hide

  • Bacterial proteolytic activity improves drug delivery in tumors in a size, pharmacokinetic, and binding affinity dependent manner – A mechanistic understanding

    Shirai H., Tsukada K.

    Journal of Controlled Release (Journal of Controlled Release)  321   348 - 362 2020.05

    ISSN  01683659

     View Summary

    © 2020 Elsevier B.V. Motile bacteria are able to penetrate in the distal areas of blood vessel, which makes bacteria attractive to researchers as a drug delivery vehicle carrying anti-cancer drugs to tumors. Not only therapeutic bacteria show wide anti-tumor effect but also the combination of therapeutic bacteria and conventional chemotherapy leads to dramatically large synergetic effect. We provide a mechanistic understanding of enhanced drug delivery in tumors by co-administration of chemotherapeutic agents and therapeutic bacteria. In this work, simultaneous delivery of C. novyi-NT and chemotherapeutic agents in tumors is mathematically modeled. Simulated doxorubicin concentration in tumors after Doxil administration with or without bacteria agreed reasonably well with experimental literature. Simulated doxorubicin concentration in tumors by the combination of Doxil and C. novyi-NT is over twice higher than that of Doxil alone. This enhanced doxorubicin concentration in tumors is due to the degradation of extracellular matrix of collagen by bacterial proteolytic activity, which increases hydraulic conductivity of interstitium, reduces interstitial fluid pressure, and thus increases convection through vessel walls. Additionally, it alleviates solid stress, which decompresses blood vessels, and thus increases vessel density. On the other hand, simulated doxorubicin concentration in tumors for non-liposomal free-doxorubicin is not enhanced by C. novyi-NT because vascular permeability of free-doxorubicin is larger than Doxil, and thus increased but relatively small convection across vessel walls is offset by the efflux due to increased interstitial flow. A strategy to further enhance this combination therapy is discussed along with sensitivity analysis.

  • High-throughput single-cell live imaging of photobiomodulation with multispectral near-infrared lasers in cultured T cells

    Katagiri W., Lee G.H., Tanushi A., Tsukada K., Choi H.S., Kashiwagi S.

    Journal of Biomedical Optics (Journal of Biomedical Optics)  25 ( 3 ) 1 - 18 2020.03

    ISSN  10833668

     View Summary

    © 2020 by ASME. Significance: Photobiomodulation is a well-established therapeutic modality. However, the mechanism of action is poorly understood, due to lack of research in the causal relationship between the near-infrared (NIR) light irradiation and its specific biological effects, hindering broader applications of this technology. Aim: Since biological chromophores typically show several absorption peaks, we determined whether specific effects of photobiomodulation are induced with a combination of two wavelengths at a certain range of irradiance only, rather than a single wavelength of NIR light. Approach: In order to analyze a wide array of combinations of multispectral NIR light at various irradiances efficiently, we developed a new optical platform equipped with two distinct wavelengths of NIR lasers by high-throughput multiple dosing for single-cell live imaging. Two wavelengths of 1064 and 1270 nm were selected based on their photobiomodulatory effects reported in the literature. Results: A specific combination of wavelengths at low irradiances (250 to 400 mW/cm2 for 1064 nm and 55 to 65 mW/cm2 for 1270 nm) modulates mitochondrial retrograde signaling, including intracellular calcium and reactive oxygen species in T cells. The time-dependent density functional theory computation of binding of nitric oxide (NO) to cytochrome c oxidase indicates that the illumination with NIR light could result in the NO release, which might be involved in these changes. Conclusions: This optical platform is a powerful tool to study causal relationship between a specific parameter of NIR light and its biological effects. Such a platform is useful for a further mechanistic study on not only photobiomodulation but also other modalities in photomedicine.

  • Respiration and Heat Shock Protein After Short-Term Heating/Stretch-Fixing on Smooth Muscle Cells

    Kaminota N., Ogawa E., Kumagai H., Tsukada K., Arai T.

    Cardiovascular Engineering and Technology (Cardiovascular Engineering and Technology)   2020

    ISSN  1869408X

     View Summary

    © 2020, Biomedical Engineering Society. Purpose: A treatment device without a stent is needed for peripheral stenotic artery treatment. We have proposed short-term heating balloon angioplasty, photo-thermo dynamic balloon angioplasty (PTDBA). Though smooth muscle cells (SMCs) after PTDBA are fixed in a stretched formation in a porcine model, influences of this stimulus on SMCs have not been investigated. SMC migration after vascular dilatation would be related to chronic restenosis. The aim of this study was to examine respiratory activity and recovery ability of SMCs after short-term heating/stretch-fixing in vitro for chronic phase treatment effect discussion. Methods: SMCs on a stretch chamber were heated for 15 s with stretching and fixed in a stretched formation. SMC migration is correlated with the cell respiratory activity. The amount of ATP production was measured using a WST-8 assay for respiratory activity evaluation. The intracellular expression of heat shock protein 70 was measured by an ELISA for recovery ability evaluation. Results: In the case of 60 °C heating, SMC respiratory activity after short-term heating/stretch-fixing decreased drastically in all stretching rates. In the case of 50 °C heating, SMC respiratory activity decreased and then increased. Alternatively, the recovery ability at 60 °C was greater than that at 50 °C. Conclusions: SMCs heated at 60 °C with stretching would have high recovery ability and low respiratory activity related to SMC migration. These results may be important evidence in determining the treatment condition in PTDBA.

  • Increasing surface-enhanced Raman scattering density using gold-coated magnetic nanoparticles controlled via a magnetic field for sensitive and efficient biomarker detection

    Shibusawa K., Hase T., Tsukada K.

    AIP Advances (AIP Advances)  9 ( 6 )  2019.06

    ISSN  2158-3226

     View Summary

    © 2019 Author(s). Early detection of various diseases is expected using surface-enhanced Raman scattering (SERS). For example, a method of labeling an antibody of a disease-related molecule on metal nanoparticles and detecting the SERS signals of the particles bound to the antigen is a promising approach. However, the problems of a slow antigen-antibody reaction and low sensitivity remain unsolved. In this study, we fabricated nanoparticles that can be freely moved using an external magnetic field for rapid antigen-antibody reaction and also nanoengineered the substrate to increase the density of hotspots required for SERS. Gold-coated magnetic nanoparticles (Au-MNPs) with a core-shell structure were prepared by applying multiple coatings of gold onto magnetic iron(II,III) oxide nanoparticles, which were used as the core. A neodymium magnet easily moved and converged the Au-MNPs in the solution within a few seconds. In addition, a silver nanoparticle substrate (Ag-NS) with a hexagonal close-packed structure fixed on a polydimethylsiloxane thin film was prepared, and the stable generation of SERS was confirmed over the entire substrate. Upon aggregation of the Au-MNPs onto Ag-NS using a neodymium magnet, the total SERS strength per unit area drastically increased, suggesting that the combination of Au-MNPs and Ag-NS increased the density of the generated hotspots. In future work, with the labeling of antibodies onto Au-MNPs, we expect the proposed method to be applied in the sensitive measurement of biomarkers associated with diseases.

  • Real-Time Imaging of Vaccine Biodistribution Using Zwitterionic NIR Nanoparticles

    Katagiri W., Lee J.H., Tétrault M.A., Kang H., Jeong S., Evans C.L., Yokomizo S., Santos S., Jones C., Hu S., Fakhri G.E., Tsukada K., Choi H.S., Kashiwagi S.

    Advanced Healthcare Materials (Advanced Healthcare Materials)  8 ( 15 ) e1900035 2019

    ISSN  21922640

     View Summary

    © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Efficient and timely delivery of vaccine antigens to the secondary lymphoid tissue is crucial to induce protective immune responses by vaccination. However, determining the longitudinal biodistribution of injected vaccines in the body has been a challenge. Here, the near-infrared (NIR) fluorescence imaging is reported that can efficiently enable the trafficking and biodistribution of vaccines in real time. Zwitterionic NIR fluorophores are conjugated on the surface of model vaccines and tracked the fate of bioconjugated vaccines after intradermal administration. Using an NIR fluorescence imaging system, it is possible to obtain time-course imaging of vaccine trafficking through the lymphatics, observing notable uptake in lymph nodes with minimal nonspecific tissue interactions. Flow cytometry analysis confirmed that the uptake in lymph nodes by antigen presenting cells was highly dependent on the hydrodynamic diameter of vaccines. These results demonstrate that the combination of a real-time NIR fluorescence imaging system and zwitterionic fluorophores is a powerful tool to determine the fate of vaccine antigens. Since such non-specific vaccine uptake causes serious adverse reactions, this method is not only useful for optimization of vaccine design, but also for safety evaluation of clinical vaccine candidates.

display all >>

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

Reviews, Commentaries, etc. 【 Display / hide

  • 皮内投与型ワクチンの免疫賦活化に適した近赤外レーザーデバイスの開発

    片桐 渉, 君塚 善文, 柏木 哲, 塚田 孝祐

    日本レーザー医学会誌 ((NPO)日本レーザー医学会)  39 ( 3 ) 254 - 254 2018.09

    ISSN  0288-6200

  • “標識しない”という新たなバイオイメージングの流れ

    塚田 孝祐

    光学 (日本光学会)  44 ( 6 ) 215 2015.06

    Introduction and explanation (scientific journal), Single Work

Presentations 【 Display / hide

  • 共焦点光学系を用いた腫瘍血管の透過性及び酸素分圧の定量化

    岩本侑一郎,小田慶太郎,塚田孝祐

    第43回レーザ顕微鏡研究会&シンポジウム, 2018.01, Oral Presentation(general)

  • 近赤外光を用いた非侵襲的ワクチンアジュバント

    柏木 哲,君塚 善文,片桐 渉,塚田 孝祐

    第38回日本レーザー医学会総会, 2017.11, Oral Presentation(general)

  • 近赤外半導体レーザーデバイスによる免疫活性化作用の検証

    片桐 渉,君塚 善文,Kashiwagi Satoshi,塚田孝祐

    第38回日本レーザー医学会総会, 2017.11, Poster (general)

  • Quantification and imaging of vascular permeability and partial pressure of oxygen in vivo

    Iwamoto Y., Oda K., Tsukada K.

    Annual Meeting of BMES 2017 (Phoenix, USA) , 2017.10, Oral Presentation(general), Biomedical Engineering Society

  • Three-dimensional in vivo analysis of histology for low-level laser therapy

    Katagiri W., Tsukada K.

    Annual Meeting of BMES 2017 (Phoenix, USA) , 2017.10, Poster (general), Biomedical Engineering Society

display all >>

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

  • 単一細胞の超解像酸素分圧イメージング

    2019.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 塚田 孝祐, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • 皮膚や臓器に貼付できるフレキシブル酸素イメージングフィルム

    2016.04
    -
    Present

    日本学術振興会, Principal Investigator

  • 近赤外光による新規ワクチンアジュバントのインフルエンザ集団予防接種への適用を目的とするポータブルレーザー医療機器の創出

    2016.04
    -
    Present

    AMED, 橋渡し研究加速ネットワークプログラム, Principal Investigator

  • 組織低酸素イメージングセンサの開発と造影剤投与不要な初期がん検出への実用

    2015.04
    -
    2016.03

    中谷医工計測技術振興財団

  • 近赤外レーザによる物理的免疫アジュバントの確立:生体の新たな光感受機構の探求

    2014.04
    -
    2015.03

    日本学術振興会, Principal Investigator

display all >>

Awards 【 Display / hide

  • Best Poster Award

    2015.09, Japanese Society for Microcirculation, A cell culture microdevice with a continuous oxygen gradient for microvascular research in vitro

  • 最優秀研究奨励賞

    佐藤安沙子,内田英幸,宮山 明,塚田孝祐, 2013.02, 日本微小循環学会, Development of a cell culture microdevice with oxygen gradient as a model for microvascular environment

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

  • 第二回先端フォトニクスシンポジウムポスター賞

    Tsukada Kosuke, 2011.10, 日本学術会議 総合工学委員会ICO分科会, 生体分光計測が解き明かすがんの低酸素・代謝メカニズム

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

Other 【 Display / hide

  •  View Details

    文部科学省スーパーグローバル大学創成支援事業による海外副指導教員の受け入れ

  •  View Details

    文部科学省スーパーグローバル大学創成支援事業による海外副指導教員の受け入れ

  •  View Details

    文部科学省スーパーグローバル大学創成支援事業による海外副指導教員の受け入れ

  •  View Details

    文部科学省スーパーグローバル大学創成支援事業による海外副指導教員の受け入れ

 

Courses Taught 【 Display / hide

  • PRACTICE IN TEACHING 2

    2021

  • PRACTICE IN TEACHING 1

    2021

  • LABORATORY IN SCIENCE

    2021

  • INDEPENDENT STUDY ON FUNDAMENTAL SCIENCE AND TECHNOLOGY

    2021

  • GRADUATE RESEARCH ON FUNDAMENTAL SCIENCE AND TECHNOLOGY 2

    2021

display all >>

Courses Previously Taught 【 Display / hide

  • 電気回路同演習

    Keio University, 2016, Spring Semester

  • 物情実験C, D

    Keio University, 2016, Autumn Semester

  • バイオメカニズム

    Keio University, 2016, Autumn Semester

  • 自然科学実験

    Keio University, 2016, Spring Semester

  • 電気回路同演習

    Keio University, 2014, Spring Semester, Lecture

display all >>

 

Social Activities 【 Display / hide

  • JSTグローバルサイエンスキャンパス

    2017.03
    -
    2018.03

     View Summary

    高校生の研究活動支援

  • JSTグローバルサイエンスキャンパス

    2014.03
    -
    2015.03

     View Summary

    高校生の研究活動支援

Memberships in Academic Societies 【 Display / hide

  • 酸素ダイナミクス研究会, 

    2015.09
    -
    Present
  • 日本微小循環学会, 

    2012.03
    -
    Present
  • 応用物理学会

     
  • 日本生体医工学会

     
  • Biomedical Engineering Society

     

display all >>

Committee Experiences 【 Display / hide

  • 2016.09
    -
    Present

    監事, 日本微小循環学会

  • 2015.09
    -
    Present

    評議委員, 酸素ダイナミクス研究会

  • 2013.04
    -
    2015.03

    論文編集委員, 計測自動制御学会

  • 2012.02
    -
    2016.08

    評議員, 日本微小循環学会

  • 2011.04
    -
    Present

    委員, 計測自動制御学会センシングフォーラム運営委員会

display all >>