NIR-ACTIVATED SILICON-RHODAMINE BASED PHOTOSENSITIZER AS A PROMISING THERAPEUTIC AGENT AGAINST GLIOBLASTOMA

Date

2024-11-01

Author

Özoğul, Naz
Karaman, Osman
Elmazoğlu, Zübeyir
Günbaş, Emrullah Görkem

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Objectives: Glioblastoma multiforme (GBM) remainsone of the most aggressive malignant tumors inthe central nervous system with low survival rate. Insufficientstandard care of the disease provoked needfor an alternative treatment. Photodynamic therapy(PDT) is a treatment modality which induces oxidativestress, leading to cell death. Our main aim is todetermine the potential anticancer effect of a novelsilicon-rhodamine-based photosensitizer N-(2-bromo-7-(dimethylamino)-5,5-dimethyl-10-(o-tolyl)dibenzo[b,e]silin-3(5H)-ylidene)-N-methylmethanaminium(2-Me-SiR-Br).Methods: U87-MG glioblastoma cells were treated for0.5-2 h followed by 4- and 6-min (650nm, 364.8mW/cm2) light irradiation in fresh medium and overnightincubation (24 h) to stimulate photodynamic effect.On the other hand, to evaluate the dark toxicity, cellswere treated for 2 h followed by overnight incubationin fresh medium (24 h) without light irradiation. MTTassay was used to determine the cytotoxicity. Subcellularlocalization in mitochondria and lysosome at 1hour was performed with confocal microscopy.Results: IC50 values of 2-Me-SiR-Br following 1-hourtreatment irradiated for 4-and 6-min with laser wasdetermined as 3.61±0.12 μM and 2.72±0.12 μM, respectively.However, the IC50 value of the agent evenafter 2-hour treatment was calculated as 15.17±0.48μM, without light irradiation. Pearson correlation1-hour incubation is 0.95 and 0.92, respectively, whichindicates localization in both organelles.Conclusions: Our findings demonstrate that 2-Me-SiR-Br exhibits dramatic phototoxicity as opposedto a weaker effect in the dark, indicating that 2-Me-SiR-Br may be a powerful PDT agent to overcomeGBM, at least in vitro. This study is supported by ERC852614 project grant.Keywords: Glioblatoma Multiforme, PDT, Cancer,Photosensitizer

URI

https://hdl.handle.net/11511/117476

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Department of Chemistry, Conference / Seminar