Lysosome-hijacking inhalable nanomimosa enhances ferroptosis for lung cancer therapy

作者：Mengqin Guo, Yiwen Liang, Meihong Zhang, Yànpíng Fù, Peili Luo, Yeqi Huang, Chuanyu Ren, Yue Gao, Xiong Si, Xia Guo, Chuanbin Wu, Xin Pan, Wenhao Wang, Zhengwei Huang · 发表于：Journal of Controlled Release · 年份：2025 · DOI：10.1016/j.jconrel.2025.114101 · 被引用次数：3 · 研究领域：Ferroptosis and cancer prognosis、Extracellular vesicles in disease、MicroRNA in disease regulation

Ferroptosis therapy shows potential for lung tumor treatment, but precise accumulation of reactive oxygen species (ROS) remains a challenge. A lysosome-hijacking strategy was developed, aiming to induce ROS spread from lysosomes to the entire cell. The key is delivering a ROS inducer to the lysosome for rapid and targeted ROS generation. In this study, transferrin (Tf) was anchored on nanomicelles to create Tf-Mic, with a coordination effect between surface carboxyl groups and Fe 3+ . The Fenton-like reaction substrate dihydroartemisinin (DHA) and system Xc- (xCT) inhibitor sorafenib (SRF) were encapsulated to form inhalable Tf-Mic@SD, or “nanomimosa,” which undergoes a conformation transition in response to stimuli. Upon inhalation, nanomimosa is captured by tumor cells through transferrin receptor (TfR) recognition, then endocytosed by lysosomes, where Tf undergoes a conformational change. This releases Fe 3+ , DHA, and SRF, causing a rapid generation of ROS. The ROS amplification accelerates ferroptosis, leading to faster tumor elimination both in vitro and in vivo . This study provides a versatile approach using lysosome-hijacking to enhance ferroptosis therapy for cancer treatment.