KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2019.04

  -

  2024.09

  慶應義塾大学, 薬学部, 特任助教

• 2024.10

  -

  Present

  慶應義塾大学, 薬学部, 助教

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 2009.04

  -

  2015.03

  Nagoya City University, 薬学部, 薬学科

• 2015.04

  -

  2019.03

  Kyoto University, 大学院薬学研究科, 薬学専攻

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• 薬剤師免許, 2015

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Nanotechnology/Materials / Nanobioscience (ドラッグデリバリーシステム)

• Nanotechnology/Materials / Chemical biology (分子イメージング)

• Life Science / Biomedical engineering (バイオマテリアル)

Books 【 Display / hide 】

Books 【 Display / hide 】

• 刺激応答性高分子の開発動向

  山田創太，金澤秀子, シーエムシー出版, 2021.07

  Scope: 第10章 9. 機能性高分子の特性を活かしたナノキャリアの開発 ,  Contact page： 191-199

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Heat-guided drug delivery via thermally induced crosslinking of polymeric micelles

  Yamada S., Sasaki E., Ohno H., Hanaoka K.

  Communications Chemistry 7   287 2024.12

  Research paper (scientific journal), Lead author, Accepted,  ISSN  23993669

  　View Summary

  Targeted drug delivery in response to external stimuli is therapeutically desirable, but long-term drug retention at the target site after stimulation is turned off remains a challenge. Herein, we present a targeted-delivery strategy via irreversible aggregation of drug carriers in response to mild external heating. We constructed two types of polymeric micelles, DBCO-TRM and Az-TRM, having a thermo-responsive polymer shell based on N-isopropylacrylamide (NIPAAm) and incorporating alkyne and azide moieties, respectively. Upon heating at 42 °C, the micelles aggregated through hydrophobic interaction between their dehydrated shells. Further, the azide moieties of Az-TRM become exposed on the surface due to the thermally shrinkage of the shells, thereby enabling crosslinking between the two types of micelles via azide-alkyne click chemistry to form irreversible aggregates. These aggregates were efficiently accumulated at tumor sites in mice by local heating after intravenous administration of a mixture of the micelles, and were well retained after cessation of heating due to their increased size. As proof of concept, we show that delivery of doxorubicin in this heat-guided drug delivery system dramatically improved the anti-tumor effect in a mouse model after a single treatment. Our results suggest that this platform could be an efficient tool for on-demand drug delivery.

  • Access to Document (DOI)

• Development of a Fluorescence Probe for Detecting Nitroreductase Activity Based on Steric Repulsion-Induced Twisted Intramolecular Charge Transfer (sr-TICT)

  Sugimoto M., Sasaki E., Ohno H., Ikeno T., Yamada S., Hanaoka K.

  Chemical and Pharmaceutical Bulletin 72 ( 9 ) 810 - 816 2024.09

  Research paper (scientific journal), Accepted,  ISSN  00092363

  　View Summary

  Twisted intramolecular charge transfer (TICT) is a phenomenon involving intramolecular charge transfer together with intramolecular rotation upon photoexcitation, and in general this excited state of fluorescent dyes undergoes non-radiative decay (producing no fluorescence). We recently discovered that the magnitude of TICT in rhodamine derivatives could be regulated by altering the size of the substituents on the xanthene moiety, generating differing degrees of intramolecular steric repulsion. To further illustrate the usefulness and generality of this strategy, we describe here an application of quinone methide chemistry, which is widely used as a fluorescence off/on switching reaction for fluorescence probes detecting enzymatic activity, to construct a steric repulsion-induced (sr)-TICT-based fluorescence probe targeting nitroreductase (NTR) activity. The developed probe was almost non-fluorescent in phosphate-buffered saline (PBS) due to strong induction of the TICT state. On the other hand, when the probe was incubated with NTR and nicotinamide adenine dinucleotide (NADH), a large fluorescence increase was observed over time. We confirmed that the enzymatic reaction proceeded as expected, i.e., the nitro group of the probe was reduced to the corresponding amino group, followed by spontaneous elimination of iminoquinone methide. These results suggest that our simple design strategy based on the sr-TICT mechanism, i.e., controlling intramolecular steric repulsion, would be applicable to the development of fluorescence probes for a variety of enzymes.

  • Access to Document (DOI)

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

  Nagase K., Kitazawa S., Kogure T., Yamada S., Katayama K., Kanazawa H.

  Separation and Purification Technology 286   120445 2022.04

  Research paper (scientific journal), Accepted,  ISSN  13835866

  　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.

  • Access to Document (DOI)

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

  Nagase K., Edatsune G., Nagata Y., Matsuda J., Ichikawa D., Yamada S., Hattori Y., Kanazawa H.

  Biomaterials Science 9 ( 21 ) 7054 - 7064 2021.11

  Research paper (scientific journal), Accepted,  ISSN  20474830

  　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. This journal is

  • Access to Document (DOI)

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

  Nagase K., Ishizawa Y., Inoue M., Kokubun M., Yamada S., Kanazawa H.

  Analytica Chimica Acta 1179   338806 2021.09

  Research paper (scientific journal), Accepted,  ISSN  00032670

  　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.

  • Access to Document (DOI)

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Recent advances in Si-rhodamine-based fluorescent probes for live-cell imaging

  Ohno H., Sasaki E., Yamada S., Hanaoka K.

  Organic and Biomolecular Chemistry 22 ( 16 ) 3099 - 3108 2024.03

  Article, review, commentary, editorial, etc. (scientific journal),  ISSN  14770520

  　View Summary

  Fluorescence imaging is a powerful technique for visualizing biological events in living samples with high temporal and spatial resolution. Fluorescent probes emitting far-red to near infrared (NIR) fluorescence are particularly advantageous for in vivo imaging due to their high tissue permeability and low autofluorescence, as well as their suitability for multicolor imaging. Among the far-red to NIR fluorophores, Si-rhodamine is one of the most practical fluorophores for the development of tailor-made NIR fluorescent probes because of the relative ease of synthesis of various derivatives, the unique intramolecular spirocyclization behavior, and the relatively high water solubility and high photostability of the probes. This review summarizes these features of Si-rhodamines and presents recent advances in the synthesis and applications of far-red to NIR fluorescent probes based on Si-rhodamines, focusing on live-cell imaging applications such as fluorogenic probes, super-resolution imaging and dye-protein hybrid-based indicators.
  

  • Access to Document (DOI)

• アルギニン密度制御によるナノ粒子の標的選択的送達

  山田 創太，佐々木 栄太，長瀬 健一，花岡 健二郎

  JSMI Report 17 ( 1 ) 25 - 29 2024.02

• ナノ粒子の構造を光で変化させて細胞挙動を制御

  山田 創太

  ファルマシア 59 ( 8 ) 775 2023.08

• 生きたマウスの組織内における一細胞イメージング

  山田 創太，樋口 ゆり子，橋田 充

  Drug delivery system 31 ( 2 ) 146 - 153 2016.03

Awards 【 Display / hide 】

Awards 【 Display / hide 】

• 第18回日本分子イメージング学会総会学術集会 優秀発表賞

  2024.05

• 第17回日本分子イメージング学会総会学術集会 優秀発表賞

  2023.06

• 第38回日本DDS学会学術集会 優秀発表賞

  2022.06

• 日本ケミカルバイオロジー学会第16回年会 ポスター賞

  2022.06

• 日本薬剤学会第33年会学生主催シンポジウム (SNPEE2018) 最優秀発表賞

  2018.05

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• 卒業研究（薬科学科）

  2024

• 分析・物理化学２

  2024

• 薬学基礎実習

  2024

• 早期体験学習（薬科学科）

  2024

• 薬剤学実習

  2024

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