慶應義塾研究者情報データベース

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• 2025年04月

  -

  継続中

  慶應義塾大学, 薬学研究科, 特任助教

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• 2017年04月

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  2023年03月

  慶應義塾大学, 薬学部, 薬学科

  卒業

• 2023年04月

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  2027年03月

  東京大学, 薬学系研究科, 薬学博士課程(4年制)

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• 薬剤師免許, 2023年03月

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• Near-infrared (NIR)-responsive activation of Ru-benziphthalocyanine complexes via singlet–triplet transition

  Takayama O., Toriumi N., Hanaoka K., Uchiyama M.

  Chemical Science 17 （ 19 ） 9600 - 9608 2026年05月

  ISSN  20416520

  　概要を見る

  Near-infrared (NIR) light-responsive molecules are important tools in life sciences due to high tissue transparency and low phototoxicity in this wavelength region. However, conventional compounds are generally activated via S<inf>0</inf>–S<inf>1</inf> transition, which requires relatively high-energy excitation. Here, in order to extend the excitation wavelength into the NIR region, we designed and synthesized Ru π-arene complexes of 6π/18π tautomeric benziphthalocyanines (BPcs), aiming to utilize the low-energy singlet–triplet transition of these complexes for activation. Experimental studies revealed that selective π-coordination of Ru to the benzene ring of BPcs disrupts the strongly NIR-absorptive, 18π-electron aromatic structure of BPcs. Nevertheless, the Ru-BPc complexes still exhibit weak and broad absorption in the NIR region, derived from singlet–triplet transition with a metal-to-ligand charge-transfer character, as indicated by theoretical calculations. NIR irradiation of Ru-BPcs at >800 nm led to efficient dissociation of Ru, releasing BPcs with strong NIR absorption and fluorescence. Thus, these complexes exhibit OFF/ON-type activation via NIR-induced Ru release due to S<inf>0</inf>–T<inf>1</inf> transition.

  • Access to Document (DOI)

• Visualizing Newly Synthesized Proteins and Their Degradation Dynamics by Using Long-Wavelength-Emitting Fluorescent Dye–DBCO Conjugates

  Sumitani S., Sasaki E., Ohno H., Yamada S., Takayama O., Wei F.Y., Kuchitsu Y., Taguchi T., Hanaoka K.

  Bioconjugate Chemistry 37 （ 5 ） 922 - 929 2026年05月

  ISSN  10431802

  　概要を見る

  Understanding the spatiotemporal dynamics of protein synthesis and degradation is important for establishing how cells maintain protein homeostasis. Conventional methods for detecting newly synthesized proteins include metabolic labeling with radioactive [³⁵S]methionine (Met) or the incorporation of l-azidohomoalanine (AHA) or l-homopropargylglycine followed by fluorescent labeling via copper(I)-catalyzed click chemistry. However, these methods typically require cell fixation, making them unsuitable for live-cell imaging. Here, we describe a fluorescence imaging technique to monitor newly synthesized proteins in living cells by utilizing a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction, in which l-AHA-containing proteins are labeled with fluorescent dyes conjugated to dibenzocyclooctyne (DBCO). We synthesized orange-emitting tetramethylrhodamine (TAMRA)-DBCO and far-red-emitting silicon rhodamine (SiR)-DBCO. TAMRA-DBCO enabled the visualization of newly synthesized proteins and their time-dependent degradation throughout the entire cell. SiR-DBCO was similarly effective, but was mainly distributed to the cytoplasm. The time-dependent decrease of TAMRA-DBCO fluorescence intensity in living cells was suppressed by lysosomal enzyme inhibitors and a proteasome inhibitor, suggesting that newly synthesized proteins are degraded via both pathways. Moreover, imaging of drug-induced senescent cells with TAMRA-DBCO suggested that senescent cells have a lower protein degradation ability than nonsenescent cells. These methods should be useful for investigating protein homeostasis in living cells.

  • Access to Document (DOI)

• Recent advances in near-infrared dye conjugates for near-infrared photoimmunotherapy (NIR-PIT): enhancing therapeutic efficacy and immune mechanisms

  Fuse Y., Sasaki E., Takayama O., Yamada S., Hanaoka K.

  Rsc Chemical Biology 2026年

  　概要を見る

  Near-infrared photoimmunotherapy (NIR-PIT) is an innovative cancer treatment modality that was approved in Japan in 2020 for the treatment of unresectable locally advanced or locally recurrent head and neck cancer. This therapy uses an antibody-dye conjugate (Ab-IR700), which consists of a monoclonal antibody targeting a specific cell-surface antigen and a phthalocyanine-based near-infrared dye, IR700, that functions as a photosensitizer. After selective accumulation in tumor tissue, Ab-IR700 is irradiated with 690 nm NIR light, which initiates a photochemical reaction that selectively damages the cell membrane of target cells, thereby inducing immunogenic cell death. Its high tumor selectivity and therapeutic efficacy establish NIR-PIT as a promising next-generation cancer therapy. However, its further application to deep-seated solid tumors remains challenging, and will require IR700 analogs and novel dye scaffolds that can be activated by longer-wavelength light to achieve greater tissue penetration and that offer greater photochemical activation efficiency. This review covers the activation mechanism of IR700, the mechanisms of cytotoxicity of NIR-PIT, emerging applications of NIR-PIT in oncology and infectious diseases, the range of dye delivery vehicles, and the development of new dyes for NIR-PIT.

  • Access to Document (DOI)

• Enzymes that generate and regulate intracellular persulfides and polysulfides: mechanistic insights and inhibitors

  Hirabayashi K., Sasaki E., Ohno H., Takayama O., Yamada S., Hanaoka K.

  Frontiers in Physiology 17 2026年

  　概要を見る

  Reactive sulfur species (RSS), which include various persulfides and polysulfides, are generated by multiple enzymes in vivo and play critical roles in mammalian physiological processes such as redox signaling, metabolic regulation, radical scavenging and anti-inflammatory responses. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) are well known to mediate endogenous production of hydrogen sulfide (H<inf>2</inf>S), and, together with the mitochondrial isoform of cysteinyl-tRNA synthetase (CARS2), are proposed to be major sources of intracellular persulfides and polysulfides. In mitochondria, enzymes involved in the sulfide oxidation pathway, including sulfide:quinone oxidoreductase (SQOR), persulfide dioxygenase (ETHE1) and thiosulfate sulfurtransferase (TST), also contribute to maintaining and regulating intracellular persulfide levels. Selective inhibitors targeting these enzymes are expected to be powerful tools for elucidating the functions of RSS, as well as having therapeutic potential. In this review, we present a comprehensive overview of these enzymes, focusing on their reaction mechanisms and inhibitors.

  • Access to Document (DOI)

• 20π-Electron Antiaromatic Benziphthalocyanines with Absorption Reaching the Near-Infrared-II Region

  Yanagi S., Takayama O., Toriumi N., Muranaka A., Hashizume D., Uchiyama M.

  Chemistry A European Journal e202400401 （ 29 ）  2024年

  研究論文（学術雑誌）, 査読有り,  ISSN  09476539

  　概要を見る

  Although second near-infrared (NIR-II, 1000–1500 nm) light has attracted considerable attention, especially for life sciences applications, the development of organic dyes with NIR-II absorption remains a formidable challenge. Herein we report the design, synthesis, and electronic properties of 20π-electron antiaromatic benziphthalocyanines (BPcs) that exhibit intense absorption bands in the NIR region. The strong, low-energy absorption of the antiaromatic BPcs is attributed to electric-dipole-allowed HOMO-LUMO transitions with narrow band gaps, enabled by the reduced structural symmetry of BPc compared with regular porphyrins and phthalocyanines. The combination of peripheral substituents and a central metal decreases the HOMO-LUMO energy gaps, leading to the extension of the absorption bands into the NIR-II region (reaching 1100 nm) under reductive conditions.

  • Access to Document (DOI)

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• フタロシアニン類縁体を用いる新たな近赤外光治療用色素の開発

  2025年07月

  -

  2027年03月

  高山 織衣, 研究活動スタート支援, 補助金,  研究代表者