期刊
BIOMEDICINES
卷 10, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/biomedicines10010134
关键词
porphyrin; chlorin; singlet oxygen; photodynamic therapy; ophiura; cancer; breast cancer; glioblastoma; mouse models
资金
- Ministry of Science and Higher Education of Russian Federation [13.1902.21.0012, 075-15-2020-796]
- Federal Research Center (FRC) of Biotechnology
Photodynamic therapy (PDT) is a powerful anticancer treatment that relies on the use of photosensitizers. This study identifies ETPA as a major metabolite of the North Pacific brittle stars and demonstrates its strong phototoxicity against cancer cell lines in vitro. In a mouse model of glioblastoma, ETPA injection combined with red laser irradiation induces necrotic ablation of the brain tumor.
Photodynamic therapy (PDT) represents a powerful avenue for anticancer treatment. PDT relies on the use of photosensitizers-compounds accumulating in the tumor and converted from benign to cytotoxic upon targeted photoactivation. We here describe (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) as a major metabolite of the North Pacific brittle stars Ophiura sarsii. As a chlorin, ETPA efficiently produces singlet oxygen upon red-light photoactivation and exerts powerful sub-micromolar phototoxicity against a panel of cancer cell lines in vitro. In a mouse model of glioblastoma, intravenous ETPA injection combined with targeted red laser irradiation induced strong necrotic ablation of the brain tumor. Along with the straightforward ETPA purification protocol and abundance of O. sarsii, these studies pave the way for the development of ETPA as a novel natural product-based photodynamic therapeutic.
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