{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:47:26Z","timestamp":1775022446052,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"the Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["25ym0126811j0004"],"award-info":[{"award-number":["25ym0126811j0004"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Meiji Seika Pharma Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Talaporfin sodium (mono-L-aspartyl chlorin e6; NPe6), a second-generation photosensitizer, is clinically used in photodynamic therapy (PDT). It accumulates preferentially in tumors and exhibits deep tissue penetration, rapid systemic clearance, and minimal photosensitivity. However, treatment of deep-seated malignancies remains challenging. Here, we demonstrate that talaporfin sodium undergoes physicochemical reactions with X-rays to generate reactive oxygen species, a mechanism analogous to that of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX in radiodynamic therapy (RDT). To evaluate its therapeutic efficacy, we employed a pancreatic cancer xenograft model using MIA PaCa-2 cells in mice. Talaporfin sodium was administered intravenously 2 h before X-ray exposure, followed by fractionated X-ray irradiation (3 Gy daily for 3 consecutive days). Talaporfin-mediated RDT significantly inhibited tumor growth compared with radiation therapy alone. Furthermore, an exploratory RNA-seq analysis of xenografts revealed transcriptional signatures of stress and immune activation, suggesting that talaporfin-mediated RDT enhances oxidative and immunogenic responses within the tumor microenvironment. These findings highlight the potential of talaporfin sodium as a clinically translatable radiosensitizer for RDT, offering a promising strategy for the treatment of deep-seated cancers such as pancreatic carcinoma.<\/jats:p>","DOI":"10.3390\/biom15121748","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:15:21Z","timestamp":1766049321000},"page":"1748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Talaporfin Sodium as a Clinically Translatable Radiosensitizer in Radiodynamic Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1941-0136","authenticated-orcid":false,"given":"Junko","family":"Takahashi","sequence":"first","affiliation":[{"name":"Graduate School of Information, Production and Systems, Waseda University, Kitakyusyu, Fukuoka 808-0135, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junkoh","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, 807-8555,  Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8343-4063","authenticated-orcid":false,"given":"Kohei","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, 807-8555,  Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2316-4828","authenticated-orcid":false,"given":"Shohei","family":"Nagasaka","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, 807-8555,  Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaizhen","family":"Yang","sequence":"additional","affiliation":[{"name":"Graduate School of Information, Production and Systems, Waseda University, Kitakyusyu, Fukuoka 808-0135, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haobo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Graduate School of Information, Production and Systems, Waseda University, Kitakyusyu, Fukuoka 808-0135, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teppei","family":"Yamaoka","sequence":"additional","affiliation":[{"name":"Graduate School of Information, Production and Systems, Waseda University, Kitakyusyu, Fukuoka 808-0135, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.rpor.2015.03.004","article-title":"Spinal metastases: From conventional fractionated radiotherapy to single-dose SBRT","volume":"20","author":"Greco","year":"2015","journal-title":"Rep. 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