Angewandte Chemie (International ed. in English) · 2026
Sequential Design of Activatable Photosensitizers for Ablation of Glioma Cells in Brain Cancer Tissues.
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Karmakar Utsa, Cheng Zhiming, Green Andrew D M, Benson Sam, Nestoros Eleni, Lim Clarissa, Cholewa-Waclaw Justyna, de Moliner Fabio, Lusarreta Paula, Seah Deborah, Bilal Alsadeg, Alfazema Neza, Aymoz-Bressot Thibaud, Morrison Gillian, Vermeren Sonja, Pollard Steven M, Brennan Paul M, Tanner Michael G, Vendrell Marc
Аннотация
Photodynamic therapy (PDT) is a promising strategy to eradicate residual glioma cells in brain cancer patients; however, current photosensitizers (PS) show limitations on selective accumulation and controlled activation in glioma cells. In this work, we present the design, synthesis, and characterization of activatable PSs for selective PDT of glioma cells in mouse and human brain tissues. First, we designed and characterized a broad collection of photosensitive metabolite conjugates, from which we prepared Gal-SeNBD-oleamide as a β-galactosidase-responsive PS with efficient uptake in patient-derived glioma cells and selectivity over immune cells. Furthermore, we optimized a whole-tissue illumination strategy using Gal-SeNBD-oleamide in mouse brain slices, which led to efficient ablation of cancer cells with minimal damage to surrounding regions. Finally, the proof-of-concept application of Gal-SeNBD-oleamide directly in tissues from brain cancer patients supports its translational potential for PDT of glioblastoma.