肿瘤治疗失败的潜在原因之一是治疗抵抗。化学治疗、放射治疗和免疫治疗的抗性仍然是临床上的主要障碍，导致肿瘤复发和转移。治疗抵抗的主要机制是通过药物失活和排泄、DNA损伤修复、肿瘤异质性或肿瘤微环境的变化等抑制细胞死亡（如细胞凋亡和坏死）。最近的研究表明，铁死亡在治疗抵抗中起着重要作用，通过诱导磷脂过氧化和依赖铁的细胞死亡。一些铁死亡诱导剂与临床治疗技术的联合应用已被用于增强肿瘤治疗效果。值得注意的是，多功能的铁死亡纳米诱导剂在逆转治疗抵抗方面具有广泛的功能，包括直接触发铁死亡和反馈调节。在此，我们提供了铁死亡介导的协同肿瘤治疗的设计、机制和治疗应用的详细描述。我们还讨论了通过调节铁死亡和联合治疗来调控肿瘤治疗抵抗方面纳米医学的前景和挑战。© 2023. 中国科学出版社。

A potential reason for the failure of tumor therapies is treatment resistance. Resistance to chemotherapy, radiotherapy, and immunotherapy continues to be a major obstacle in clinic, resulting in tumor recurrence and metastasis. The major mechanisms of therapy resistance are inhibitions of cell deaths, like apoptosis and necrosis, through drug inactivation and excretion, repair of DNA damage, tumor heterogeneity, or changes in tumor microenvironment, etc. Recent studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell death. Some ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor therapy. Notably, versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance, including directly triggering ferroptosis and feedback regulation. Herein, we provide a detailed description of the design, mechanism, and therapeutic application of ferroptosis-mediated synergistic tumor therapeutics. We also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.© 2023. Science China Press.