IODINATED SI-FLUORESCEIN BASED PHOTOSENSITIZER AS A THERANOSTIC AGENT AGAINST HUMAN GLIOBLASTOMA CELLS

Date

2024-06-28

Author

Kepil, Dilay
Karaman, Osman
Günbaş, Emrullah Görkem

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Introduction:Glioblastoma (GBM), which is a highly aggressive and lethal type of glioma, remains a significant challenge in modern medicine. Photodynamic therapy (PDT) is an emerging light-based alternative approach with several advantages, including high efficiency, minimal invasiveness, and a lack of side effects compared to traditional treatments like chemotherapy and radiotherapy. In PDT applications, fluorescein-based photosensitizers are commonly used due to their water solubility, photostability, and ease of modification for improvement towards the near-infrared region with enhanced photochemical properties for deep tissue applications. β-galactosidase (β-gal) is a popular biomarker overexpressed in several cancer types, including gliomas. Herein, we investigated β-gal activatable Si-fluorescein-based phototheronastic agent for treating brain cancer. Materials and Methods: Human glioblastoma (U87MG) and mouse fibroblast (L929) cells were used to test an enzyme-activating PDT agent, β-GalSiF-II. To determine toxicity of β-Gal-SiF-II, both U87MG and L929 cells were treated with β-Gal-SiF-II (0 -10 μM) for 24 hours (dark) or 1hfollowed by illumination at 595 nm (9.38 mW/cm², 2 h). MTT analysis was held either with or without scavengers of: N-acetylcysteine, mannitol, trolox or sodium azide. DCFDA, AO/EtBr staining and subcellular localization assays were performed with confocal microscopy. Results: Our findings indicated that β-Gal-SiF-II reduced cell viability of U87MG (IC50: 3.301µM) significantly whereas it showed less cytotoxicity in L929 healthy cells (IC50: 6.270µM) under light irradiation. Mitochondrial and lysosomal localization of activated β-Gal-SiF-II led to elevated ROS generation and apoptotic cell death which was confirmed by DCFDA and AO/ EtBr staining, respectively. Conclusions:The enzyme-activating PDT agent, β-Gal-SiF-II, has the potential to advance brain cancer treatment and diagnostics.

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https://isops-ankara.org/wp-content/uploads/2024/10/ISOPS-EBook.pdf
https://hdl.handle.net/11511/117719

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Department of Chemistry, Conference / Seminar