体内
胶质瘤
体外
药理学
癌症研究
U87型
化学
医学
生物
生物化学
生物技术
作者
Catalina Alamón,Belén Dávila,María Fernanda García,S. Nievas,María Alejandra Dagrosa,Silvia I. Thorp,Mariángeles Kovacs,Emiliano Trías,Ricardo Faccio,Martín Gabay,Nidal Zeineh,Abraham Weizman,Francesç Teixidor,Clara Viñas,Moshe Gavish,Hugo Cerecetto,Marcos Couto
标识
DOI:10.1021/acs.molpharmaceut.3c00152
摘要
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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