慶應義塾研究者情報データベース

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• 2019年04月

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  2024年09月

  慶應義塾大学, 薬学部, 特任助教

• 2024年10月

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  継続中

  慶應義塾大学, 薬学部, 助教

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• 2009年04月

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  2015年03月

  名古屋市立大学, 薬学部, 薬学科

• 2015年04月

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  2019年03月

  京都大学, 大学院薬学研究科, 薬学専攻

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• 薬剤師免許, 2015年

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• ナノテク・材料 / ナノバイオサイエンス （ドラッグデリバリーシステム）

• ナノテク・材料 / ケミカルバイオロジー （分子イメージング）

• ライフサイエンス / 生体医工学 （バイオマテリアル）

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• 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年07月

  担当範囲: 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 ,  担当ページ： 191-199

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• Thermo-responsive targeting of polymeric micelles by controlling the cellular uptake based on the change of their surface arginine density.

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

  Communications Chemistry 8   325 2025年11月

  研究論文（学術雑誌）, 筆頭著者, 査読有り,  ISSN  23993669

  　概要を見る

  Stimulus-responsive nanocarriers are good candidates for targeted drug delivery. Herein, inspired by the existence of a clear threshold number of arginine residues in oligoarginines for cell-penetrating peptide (CPP) activity, we developed a strategy to control the CPP activity by changing the local arginine density for thermo-responsive targeting. We constructed polymeric micelles whose shell consists of a thermo-responsive polymer based on N-isopropylacrylamide, with a low density of arginine moieties (named Arg-TRM). At physiological temperature (37 °C), internalization of Arg-TRM into cells was small and comparable to that of micelle without arginine. In contrast, upon heating at 42 °C, the arginine density on the micellar surface was increased by thermo-responsive shrinkage of the shell, thereby switching on the CPP activity and enabling efficient cellular uptake. The response of Arg-TRM at 42 °C occurred within a few minutes and the intracellular uptake was rapidly enhanced from 5 min after the heating. This response was transient, thus enabling reversible control of the enhancement by heating. As proof-of-concept, we show that intravenously administered Arg-TRM was effectively accumulated in one ear of a normal mouse by local heating. These results indicate that Arg-TRM is a promising drug carrier for on-demand targeted drug delivery in response to mild external heating.

  • Access to Document (DOI)

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

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

  Communications Chemistry 7 （ 1 ） 287 2024年12月

  研究論文（学術雑誌）, 筆頭著者, 査読有り,  ISSN  23993669

  　概要を見る

  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. (Figure presented.)

  • Access to Document (DOI)

• Development of a silicon phthalocyanine analogue for near-infrared photoimmunotherapy and its application to HTLV-1-infected leukemic cells

  Fuse Y., Sasaki E., Tamaki M., Kawamura S., Ohno H., Yamada S., Yasunaga M., Takakura H., Hanaoka H., Kobayashi H., Nakasone H., Hanaoka K.

  Rsc Chemical Biology 6 （ 10 ） 1576 - 1584 2025年10月

  研究論文（学術雑誌）, 査読有り

  　概要を見る

  Near-infrared photoimmunotherapy (NIR-PIT) employing an antibody labeled with a silicon phthalocyanine dye, IR700, was approved as a minimally invasive treatment for unresectable recurrent head and neck cancer in Japan in 2020. However, further derivatization of IR700 is needed to increase the efficiency of cancer treatment. Here, we developed SiPc-1 as an IR700 analog, in which the linker was constructed using click chemistry to simplify the synthetic scheme and its position was switched from α to β on the benzene ring of phthalocyanine to eliminate intramolecular steric repulsion. We evaluated the cleavage rate of the water-soluble axial moieties of SiPc-1 upon photoirradiation, the cytotoxicity, and the morphological change (blebbing) of treated cells upon photoirradiation. We performed gene expression and protein expression analyses to find a target antigen selectively expressed on cells infected with human T-cell lymphotropic virus type 1 (HTLV-1), the causative virus of adult T-cell leukemia/lymphoma (ATL), and identified CD25 as a suitable target antigen. An anti-CD25 antibody, basiliximab, labeled with SiPc-1 (bas-SiPc-1) showed selective toxicity towards HTLV-1-infected cultured cells and ATL patients’ peripheral blood mononuclear cells upon photoirradiation.

  • Access to Document (DOI)

• Trans-omics landscape of systemic vasculitis identified matrix metalloproteinase 12 as a novel signature molecule

  Matsumoto K., Suzuki K., Magi M., Onishi S., Yoshida H., Takeshita M., Kuramoto J., Yazawa M., Kato T., Shimizu H., Ito T., Yamada S., Sasaki E., Hanaoka K., Noguchi-Sasaki M., Matsumoto Y., Takeuchi T., Kaneko Y.

  Rheumatology 64 （ 8 ） 4766 - 4775 2025年08月

  研究論文（学術雑誌）, 査読有り,  ISSN  14620324

  　概要を見る

  Objectives To identify key molecules involved in the disease pathophysiology of systemic vasculitis through trans-omics analysis, with a specific focus on demonstrating matrix metalloproteinase (MMP) 12 as a potential biomarker in rheumatic entities. Methods Patients with newly diagnosed or relapsed rheumatic and musculoskeletal diseases from June 2013 until September 2022 were enrolled. We screened vasculitis-specific molecules by combining findings from serum proteome analysis and whole-blood RNA sequencing. We further validated the identified molecules using immunohistochemical staining and spatial transcriptome analysis. Results Serum proteome and RNA sequencing identified MMP12 as a significant molecule for systemic vasculitis; it distinguished vasculitis from other rheumatic and musculoskeletal diseases, reflected disease activity along with longitudinal change, and predicted relapse in patients with large-vessel vasculitis. MMP12 could also be used to detect insidious disease activity even under treatment with IL-6 inhibition. Immunohistochemical staining of the affected tissues demonstrated that MMP12 was specifically expressed in tissue-infiltrating CD206-positive macrophages. Spatial transcriptome analysis revealed the characteristic phenotype of MMP12-positive macrophages and its association with macrophage maturation and formation of multinucleated giant cells. Conclusion MMP12 is a disease-specific molecule that is associated with macrophage maturation and the formation of multinucleated giant cells and reflects disease activity independently of the IL-6 pathway in systemic vasculitis.

  • Access to Document (DOI)

• Development of a near-infrared fluorescence probe for hypochlorous acid based on the phenyl-induced twisted intramolecular charge transfer (p-TICT) mechanism

  Ohno H., Sumitani S., Chuluun-Erdene A., Kuchimaru T., Yamada S., Sasaki E., Hanaoka K.

  Chemical Communications 61 （ 57 ） 10522 - 10525 2025年06月

  研究論文（学術雑誌）, 査読有り,  ISSN  13597345

  　概要を見る

  Near-infrared (NIR) fluorescence probes for hypochlorous acid (HClO) are powerful tools for investigating various biological phenomena because of their low autofluorescence, high tissue penetration and usefulness for multicolour imaging. Here we present a rational probe design strategy based on the phenyl-induced twisted intramolecular charge transfer (p-TICT) mechanism and apply it to develop a NIR fluorescence probe for HClO, N-Phenol SiR1. This probe was applied for multicolor (4 colors) live-cell fluorescence imaging, occupying the NIR color window.

  • Access to Document (DOI)

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• Recent advances in fluorogenic probes based on twisted intramolecular charge transfer (TICT) for live-cell imaging

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

  Chemical Communications 61 （ 69 ） 12871 - 12884 2025年08月

  記事・総説・解説・論説等（学術雑誌）,  ISSN  13597345

  　概要を見る

  Fluorescence imaging is a powerful technique for visualizing biological events in living samples, and new fluorescence-control mechanisms are still needed to extend the scope of biomolecule-targeting fluorogenic probes. Twisted intramolecular charge transfer (TICT) is a unique fluorescence quenching mechanism that depends upon a twisted conformation to promote intramolecular charge separation. Probes utilizing TICT can detect biological molecules/phenomena, such as viscosity, polarity and extended protein structures, that cannot readily be accessed by probes employing other fluorescence-control mechanisms, such as photoinduced electron transfer or spirocyclization. In this review, we summarize recent work on molecular design strategies for TICT-based fluorogenic probes, focusing on structural-modification approaches to control the ease of TICT state formation.
  

  • Access to Document (DOI)

• 熱に応答した架橋形成によるナノ粒子の標的選択的送達

  山田 創太，花岡 健二郎

  JSMI Report 18 （ 1 ） 31 - 35 2025年02月

  筆頭著者

• 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年03月

  記事・総説・解説・論説等（学術雑誌）,  ISSN  14770520

  　概要を見る

  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年02月

  筆頭著者

• 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年08月

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• 第37回バイオメディカル分析科学シンポジウム 星野賞 研究奨励賞

  2025年08月

• 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年05月

• 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年06月

• 第38回日本DDS学会学術集会 優秀発表賞

  2022年06月

• 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年06月

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• 卒業研究１（薬学科）

  2025年度

• 薬剤学実習

  2025年度

• 英語演習（薬学科）

  2025年度

• 物質機能化学特論

  2025年度

• 英語演習（薬科学科）

  2025年度

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