Li Xuejing, Wu Jiayi, Xu Ruizhe, Qin Xifeng, Wang Siyu, Yang Wuli, Pang Zhiqing
Key Laboratory of Smart Drug Delivery, School of Pharmacy, Fudan University, Shanghai 201203, China.
State Key Laboratory of Molecular Engineering of Polymers & Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
Acta Pharm Sin B. 2025 Jul;15(7):3788-3804. doi: 10.1016/j.apsb.2025.05.006. Epub 2025 May 28.
Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.
冷肿瘤由于免疫细胞浸润少以及具有逃避免疫攻击的能力，对肿瘤免疫疗法反应不佳。将冷肿瘤转变为热肿瘤可提高抗肿瘤免疫疗法的临床疗效。高强度聚焦超声（HIFU）作为一种非侵入性治疗方法，可通过机械效应损伤肿瘤，但在细胞水平上其细胞毒性机制及其在诱导抗免疫反应中的作用缺乏研究。在本研究中，研究了HIFU通过机械化学作用破坏谷胱甘肽/氧化型谷胱甘肽（GSH/GSSG）平衡触发肿瘤铁死亡的作用以及相关的抗肿瘤免疫启动效应。使用负载全氟溴辛烷（PFOB）的纳米增强剂与HIFU相结合，可在肿瘤生长的特定阶段（UTGR = 0）增强三阴性乳腺癌中的铁死亡，同时促进冷肿瘤向热肿瘤的转变，从而改善免疫反应。总体而言，这为HIFU在肿瘤免疫治疗中的临床应用提供了有价值的指导。
