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Reactive oxygen species activated by mitochondria-specific camptothecin prodrug for enhanced chemotherapy

Camptothecin (CPT) has attracted much attention due to its potent antitumor activities. However, the undesirable physicochemical properties, including poor water solubility, unstable lactone ring, and severe adverse effects, limit its further application. In this study, two water-soluble prodrugs, C...

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Detalles Bibliográficos
Autores principales: Guo, Zhaopei, Wang, Zian, Liang, Ruifeng, Tian, Huayu, Chen, Xuesi, Chen, Meiwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589304/
https://www.ncbi.nlm.nih.gov/pubmed/35801419
http://dx.doi.org/10.17305/bjbms.2022.7194
Descripción
Sumario:Camptothecin (CPT) has attracted much attention due to its potent antitumor activities. However, the undesirable physicochemical properties, including poor water solubility, unstable lactone ring, and severe adverse effects, limit its further application. In this study, two water-soluble prodrugs, CPT-lysine and CPT-arginine, were designed and synthesized by conjugating lysine or arginine with CPT, improving its solubility, pharmacokinetic properties, and tumor penetration. Importantly, the introduction of arginine into CPTR contributed to the mitochondria-specific delivery, which increased mitochondrial reactive oxygen species generation, induced mitochondria dysfunction, and enhanced cell apoptosis and in vivo anti-cancer effect. This strategy is believed to hold great potential for organelle-specific synergistic anti-tumor therapy.