尽管放射治疗对食管鳞状细胞癌（ESCC）具有卓越的疗效，但癌症干细胞（CSC）的放射抗性会导致复发、转移和治疗失败。因此，有必要开发基于CSC的疗法来增强放射治疗。基于 ESCC 队列，miR-339-5p (miR339) 参与干细胞分裂和 DNA 损伤检查点信号通路。 miR339 通过靶向 USP8 抑制 ESCC 细胞干性并增强辐射诱导的 DNA 损伤，表明它作为潜在的 CSC 调节剂和放射增敏剂。考虑到miRNA的循环周期有限和肿瘤靶向能力差，开发了基于硫化铋纳米花（Bi@PP）的多功能纳米平台，以有效递送miR339并提高放射抗性。有趣的是，Bi@PP 由于其花形结构而封装了更多的 miR339，将超过 1000 倍的 miR339 递送到细胞中，优于单独的游离 miR339。除了用作载体外，Bi@PP 还有利于动态监测体内递送的 miR339 的分布，同时抑制肿瘤生长。此外，Bi@PP/miR339 可以显着增强患者来源的异种移植模型的放疗效果。这个多功能平台结合了更高的 miRNA 负载能力、pH 响应性、缺氧缓解和 CT 成像，提供了另一种提高放射敏感性和优化 ESCC 治疗的方法。

Despite the superior efficacy of radiotherapy in esophageal squamous cell carcinoma (ESCC), radioresistance by cancer stem cells (CSCs) leads to recurrence, metastasis, and treatment failure. Therefore, it is necessary to develop CSC-based therapies to enhance radiotherapy. miR-339-5p (miR339) is involved in stem cell division and DNA damage checkpoint signaling pathways based on ESCC cohort. miR339 inhibited ESCC cell stemness and enhanced radiation-induced DNA damage by targeting USP8, suggesting that it acts as a potential CSC regulator and radiosensitizer. Considering the limited circulating periods and poor tumor-targeting ability of miRNA, a multifunctional nanoplatform based on bismuth sulfide nanoflower (Bi@PP) is developed to efficiently deliver miR339 and improve radioresistance. Intriguingly, Bi@PP encapsulates more miR339 owing to their flower-shaped structure, delivering more than 1000-fold miR339 into cells, superior to free miR339 alone. Besides being used as a carrier, Bi@PP is advantageous for dynamically monitoring the distribution of delivered miR339 in vivo while simultaneously inhibiting tumor growth. Additionally, Bi@PP/miR339 can significantly enhance radiotherapy efficacy in patient-derived xenograft models. This multifunctional platform, incorporating higher miRNA loading capacity, pH responsiveness, hypoxia relief, and CT imaging, provides another method to promote radiosensitivity and optimize ESCC treatment.