TRAIL-driven targeting and reversing cervical cancer radioresistance by seleno-nanotherapeutics through regulating cell metabolism

• Published in: Drug resistance updates 2024-01, Vol.72, p.101033-101033, Article 101033
• Main Authors: Jiang, Wenxiao, Huang, Guanning, Pan, Shuya, Chen, Xin, Liu, Ting, Yang, Ziyi, Chen, Tianfeng, Zhu, Xueqiong
• Format: Article
• Language: English
• Subjects: Apoptosis; Cell Line, Tumor; Female; Humans; Hydrogen Peroxide; Ligands; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; TNF-Related Apoptosis-Inducing Ligand - metabolism; TNF-Related Apoptosis-Inducing Ligand - pharmacology; Tumor Microenvironment; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - radiotherapy
• ISSN: 1368-7646; 1532-2084
• DOI: 10.1016/j.drup.2023.101033

Recently, radioresistance has become a major obstacle in the radiotherapy of cervical cancer. To demonstrate enhanced radiosensitization against radioresistant cervical cancer, radioresistant cervical cancer cell line was developed and the mechanism of radioresistance was explored. Due to the overexpression of (death receptor 5, DR5) in cervical cancer, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-overexpressed cervical cancer cell membrane-camouflaged Cu Se nanomedicine (CCMT) was designed. Since the CCMT was encapsulated with TRAIL-modified cell membrane, it represented high target to cervical cancer cell and immune evasion. Furthermore, Cu Se had the ability to scavenge glutathione (GSH) and produce ·OH with excess H O in the tumor microenvironment. The presence of CCMT combined with radiation therapy could effectively increase the O produced by X-rays. In vitro and in vivo studies elaborated that CCMT exhibited excellent radiosensitization properties to reverse radiotolerance by scavenging GSH and promoting DNA damage, apoptosis, mitochondrial membrane potential damage and metabolic disruption. Collectively, this study suggested that the development of TRAIL-overexpressed cell membrane-camouflaged Cu Se nanomedicine could advance future cervical cancer treatment and minimize the disadvantages associated with radiation treatment.