A Potential Boron Neutron Capture Therapy Agent Selectively Suppresses High-Grade Glioma: In Vitro and in Vivo Exploration

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...

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Detalles Bibliográficos
Autores: 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, Viñas, Clara, Gavish, Moshe, Cerecetto, Hugo, Couto, Marcos
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/329781
Acceso en línea:http://hdl.handle.net/10261/329781
https://api.elsevier.com/content/abstract/scopus_id/85153614910
Access Level:acceso abierto
Palabra clave:Boron neutron capture therapy
Epidermal growth factor receptors
Glioblastoma
Descripción
Sumario: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.

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