Photodynamic Therapy against Glioblastoma: Investigating phenoselenazine based photosensitizer as a promising therapeutic agent

Date

2024-11-01

Author

Yeşilçimen, Elif
Karaman, Osman
Elmazoğlu, Zübeyir
Günbaş, Emrullah Görkem

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Objectives: Glioblastoma Multiforme (GBM) is themost aggressive malignant brain tumor. Photodynamictherapy (PDT) is a promising treatment strategyagainst GBM. It exerts cytotoxic effect by producingROS, mainly singlet oxygen, leading to cell death. Theaim of the present study was to investigate the efficacyof a novel phenoselenazine based photosensitizer1-(7-(azetidin-1-yl)-3H-phenoselenazin-3-ylidene)azetidin-1-ium (NSeAze) with NIR light irradiationon glioblastoma cells.Methods: U-87MG and U-118MG glioblastoma cellswere treated with NSeAze for 24h to assess its darktoxicity. For PDT application, cells were treated for2h and exposed to 660-670 nm LED light for 1h, thenincubated overnight up to 24h in the dark. The cell viabilitywas detected with MTT assay following NSe-Aze administration with/without the presence of scavengers.The subcellular localization in mitochondria/lysosomes was visualized by confocal microscopy.Results: Results showed a significant reduction in cellviability with IC50 of 376.3±17.85 nM and 531.7±25.53nM in U-87MG and U-118MG cells, respectively. Thephototoxicity index (PI) was determined as 472.49and 72.89, indicating the remarkable effect of NSeAzeunder light irradiation. The scavenger assay confirmedthat NSeAze induces oxidative stress by producingmostly singlet oxygen. The subcellular localizationshowed that the agent predominantly accumulates inlysosomes, with a strong Pearson correlation value of0.78, compared to mitochondria (0.69).Conclusions: The present study showed that the novelphotosensitizer NSeAze has significant antitumor activityas a PDT agent against glioblastoma cells, indicatingthat it may be a promising therapeutic agent inthe treatment. This study is supported by ERC 852614project grant.Keywords: Photodynamic Therapy, Oxidative Stress,Glioblastoma Multiforme, Cancer, Photosensitizer

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https://2024.biyokimyakongresi.org/panel/datas/genel/files/bclf2024_abstract_book.pdf
https://hdl.handle.net/11511/117511

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Department of Chemistry, Conference / Seminar