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

Wenxiao Jiang; Guanning Huang; Shuya Pan; Xin Chen; Ting Liu; Ziyi Yang; Tianfeng Chen; Xueqiong Zhu

doi:10.1016/j.drup.2023.101033

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

Drug Resist Updat. 2024 Jan:72:101033. doi: 10.1016/j.drup.2023.101033. Epub 2023 Dec 9.

Authors

Wenxiao Jiang¹, Guanning Huang², Shuya Pan¹, Xin Chen¹, Ting Liu¹, Ziyi Yang¹, Tianfeng Chen³, Xueqiong Zhu⁴

Affiliations

¹ Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
² State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, Department of Chemistry, Jinan University, Guangzhou 510632, China.
³ Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, Department of Chemistry, Jinan University, Guangzhou 510632, China. Electronic address: tchentf@jnu.edu.cn.
⁴ Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: zjwzzxq@163.com.

PMID: 38157648
DOI: 10.1016/j.drup.2023.101033

Abstract

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_2-xSe 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_2-xSe had the ability to scavenge glutathione (GSH) and produce ·OH with excess H₂O₂ in the tumor microenvironment. The presence of CCMT combined with radiation therapy could effectively increase the ¹O₂ 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_2-xSe nanomedicine could advance future cervical cancer treatment and minimize the disadvantages associated with radiation treatment.

Keywords: Cell membrane; Cell metabolism; Cervical cancer; Cu(2−x)Se; Radioresistance; TRAIL.

MeSH terms

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

Substances

Hydrogen Peroxide
Ligands
Receptors, TNF-Related Apoptosis-Inducing Ligand
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha