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Título: | A Potential Boron Neutron Capture Therapy Agent Selectively Suppresses High-Grade Glioma: In Vitro and in Vivo Exploration |
Autor: | Alamón, Catalina; Dávila, Belén; García, María Fernanda; Nievas, Susana; Dagrosa, María Alejandra; Thorp, Silvia; Kovacs, Mariángeles; Trias, Emiliano; Faccio, Ricardo; Gabay, Martín; Zeineh, Nidal; Weizman, Abraham; Teixidor, Francesc CSIC ORCID; Viñas, Clara CSIC ORCID; Gavish, Moshe; Cerecetto, Hugo; Couto, Marcos | Palabras clave: | Boron neutron capture therapy Epidermal growth factor receptors Glioblastoma |
Fecha de publicación: | 4-abr-2023 | Editor: | American Chemical Society | Citación: | Molecular Pharmaceutics 20(5): 2702-2713 (2023) | Resumen: | Glioblastoma (GBM), as the most central nervous system (CNS) intractable disease, has spoiled millions of lives due to its high mortality. Even though several efforts have been made, the existing treatments have had limited success. In this sense, we studied a lead compound, the boron-rich selective epidermal growth factor receptor (EGFR)-inhibitor hybrid 1, as a potential drug for GBM treatment. For this end, we analyzed the in vitro activity of hybrid 1 in a glioma/primary astrocytes coculture, studying cellular death types triggered by treatment with this compound and its cellular localizations. Additionally, hybrid 1 concentrated boron in glioma cells selectively and more effectively than the boron neutron capture therapy (BNCT)-clinical agent 10B-l-boronophenylalanine and thus displayed a better in vitro-BNCT effect. This encouraged us to analyze hybrid 1 in vivo. Therefore, immunosuppressed mice bearing U87 MG human GBM were treated with both 1 and 1 encapsulated in a modified liposome (recognized by brain-blood barrier peptide transporters), and we observed a potent in vivo per se antitumor activity (tumor size decrease and animal survival increase). These data demonstrate that 1 could be a promising new targeted therapy for GBM. | Versión del editor: | http://doi.org/10.1021/acs.molpharmaceut.3c00152 | URI: | http://hdl.handle.net/10261/329781 | DOI: | 10.1021/acs.molpharmaceut.3c00152 | ISSN: | 1543-8384 |
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