Akademik Veri Yönetim Sistemi
Pharmaceutics, cilt.18, sa.4, 2026 (SCI-Expanded, Scopus)
Background: Photodynamic therapy (PDT) offers a promising complementary strategy for treating glioblastoma multiforme (GBM); however, limited control over photosensitizer activation and reduced efficacy under hypoxic conditions remain significant limitations. Methods: In this study, we present the synthesis and functional evaluation of Gal-SiX, an enzymatically activatable Si-xanthene-based activatable PDT agent designed to address these challenges. Prepared via an improved 10-step synthetic route, Gal-SiX exhibits clear turn-on fluorescence and absorbance responses upon β-galactosidase activation and efficiently generates reactive oxygen species in aqueous media. Results: Mechanistic studies revealed that Gal-SiX enables both Type I and Type II PDT pathways, a favorable feature for GBM environments characterized by restricted oxygen availability. In vitro assays conducted on U87MG glioblastoma cells and L929 healthy fibroblasts demonstrated light-dependent cytotoxicity, with IC50 values of 3.30 μM and 7.19 μM, respectively. Gal-SiX also showed minimal dark toxicity (>80 μM) and potent light-induced cytotoxicity, yielding a phototoxicity index of 24.8 in glioblastoma cells. Confocal imaging and MTT assays consistently confirmed enzymatic activation and effective PDT response at the cellular level. Conclusions: Overall, this work introduces the first activatable Si-xanthene-based PDT agent for glioblastoma and provides the first evidence that the Si-xanthene scaffold can support dual Type I/II phototoxicity. These results underscore Gal-SiX’s potential as a PDT platform for addressing the unique constraints of GBM biology.