Nanocarriers Targeting Circular RNA ADARB1 Boost Radiosensitivity of Nasopharyngeal Carcinoma through Synergically Promoting Ferroptosis

作者：Dan Wang, Le Tang, Mingjian Chen, Zhaojian Gong, Chunmei Fan, Hongke Qu, Yixuan Liu, Lei Shi, Yongzhen Mo, Yumin Wang, Qijia Yan, Pan Chen, Bo Xiang, Qianjin Liao, Zhaoyang Zeng, Guiyuan Li, Weihong Jiang, Xu Wu, Wei Xiong · 发表于：ACS Nano · 年份：2024 · DOI：10.1021/acsnano.4c07676 · 被引用次数：32 · 研究领域：Circular RNAs in diseases、Cancer-related molecular mechanisms research、RNA modifications and cancer

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck, prevalent in regions such as Southern China and Southeast Asia. Radiotherapy serves as the primary clinical treatment for this carcinoma. However, resistance to radiotherapy is a fundamental cause of treatment failure and patient mortality, with the underlying mechanisms yet to be fully elucidated. We identified a recently characterized circular RNA, circADARB1, which is markedly upregulated in NPC tissues and closely associated with poor prognosis and radiotherapy resistance. Both in vitro and in vivo experiments demonstrated that circADARB1 inhibited ferroptosis, thereby inducing radiotherapy resistance in NPC cells. Building on these findings, we synthesized a biomimetic nanomaterial consisting of semiconducting polymer nanoparticles wrapped in cell membranes, designed to deliver both siRNA targeting circADARB1 and iron ions. The application of this nanomaterial not only efficiently suppressed the expression of circADARB1 and boosted intracellular iron concentrations, but also enhanced ferroptosis induced by radiotherapy, improving the radiosensitivity of NPC cells. Furthermore, our study revealed that circADARB1 upregulated the expression of heat shock protein HSP90B1, which repaired misfolded SLC7A11 and GPX4 proteins triggered by radiotherapy, thereby preserving their stability and biological functions. Mechanistically, SLC7A11 facilitated cysteine transportation into cells and glutathione ...