Drastic Impact of Donor Substituents on Xanthenes in the PDT of Glioblastoma

Date

2025-10-01

Author

Karaman, Osman
Yesilcimen, E.
Forough, M.
Elmazoglu, Z.
Günbaş, Emrullah Görkem

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Even though significant progress has been made in treating various cancer types, brain cancers lag drastically. Several factors contribute, led by operational difficulties, the blood-brain barrier, and the tendency of recurrence. Alternative therapies are needed, and photodynamic therapy (PDT) offers several advantages. However, PDT has rarely been explored for brain cancers since, for achieving near-infrared range activation, photosensitizers should have longer conjugation lengths and thus higher molecular weight, which then limits blood-brain barrier penetration. Here, we describe the syntheses and PDT action of two new selenium-containing xanthane-based photosensitizers (NSeMorph and NSeAze) that show absorption over 650 nm with molecular weights lower than 420 g/mol. It has been demonstrated that both NSeMorph and NSeAze showed PDT activity against glioblastoma cell lines (U87MG and U118MG), and more interestingly, the efficacy and selectivity of the photosensitizers were significantly different depending on the donor side groups. NSeMorph, utilizing morpholine donors, showed IC50 values of 15.8 mu M for U87MG and 8.0 mu M for U118MG cell lines. Surprisingly, the IC50 was not reached at a 20 mu M concentration in the healthy cell line (L929), indicating the selective nature of NSeMorph even though no activation-based cage groups or targeting groups were present. Upon switching the donor units to azetidine, IC50 values of 456 nM for U87MG and 461 nM for U118MG cell lines were achieved; to the best of our knowledge, these are the lowest IC50 values reported in literature against glioblastoma (U87MG and U118MG) that combine NIR absorption in aqueous media and low molecular weight (<400 g/mol). Additionally, NSeAze showed one of the highest phototoxicity indices, the ratio of cell viabilities under dark and light conditions, showing the remarkable activity of NSeAze under illumination. Overall, this study represents one of the first examples of the drastic effect on PDT action by altering only the donor side groups of xanthene-based dyes.

URI

https://hdl.handle.net/11511/117013

Collections

Department of Chemistry, Article