Abstract：
Ferroptosis, a form of regulated cell death characterized by iron-dependent phospholipid peroxidation, has emerged as a focal point in the field of cancer therapy. Compared with other cell death modes such as apoptosis and necrosis, ferroptosis exhibits many distinct characteristics in the molecular mechanisms and cell morphology, offering a promising avenue for combating cancers that are resistant to conventional therapeutic modalities. In light of the serious side effects associated with current Fenton-modulating ferroptosis therapies utilizing exogenous iron-based inorganic nanomaterials, hijacking endogenous iron could serve as an effective alternative strategy to trigger ferroptosis through targeting cellular iron regulatory mechanisms. A better understanding of the underlying iron regulatory mechanism in the process of ferroptosis has shed light on the current findings of endogenous ferroptosis-based nanomedicine strategies for cancer therapy. Here in this review article, we provide a comprehensive discussion on the regulatory network of iron metabolism and its pivotal role in ferroptosis, and present recent updates on the application of nanoparticles endowed with the ability to hijack endogenous iron for ferroptosis. We envision that the insights in the study may expedite the development and translation of endogenous ferroptosis-based nanomedicines for effective cancer treatment.
摘要：
Ferroptosis,一种以铁依赖性磷脂过氧化为特征的调节性细胞死亡形式，已经成为癌症治疗领域的焦点。与其他细胞死亡模式如凋亡和坏死相比，铁凋亡在分子机制和细胞形态学上表现出许多不同的特征，提供了一个有希望的途径来对抗对传统治疗方式有抵抗力的癌症。鉴于与当前使用外源性铁基无机纳米材料的Fenton调节铁性凋亡疗法相关的严重副作用，劫持内源性铁可以作为一种有效的替代策略，通过靶向细胞铁调节机制来触发铁凋亡。对铁凋亡过程中潜在的铁调节机制的更好理解已经揭示了基于内源性铁凋亡的癌症治疗纳米医学策略的最新发现。在这篇评论文章中，我们对铁代谢的调节网络及其在铁凋亡中的关键作用进行了全面的讨论，并介绍了具有劫持内源性铁以实现铁凋亡能力的纳米颗粒的最新应用。我们设想，该研究中的见解可能会加速内源性基于铁凋亡的纳米药物的开发和翻译，以用于有效的癌症治疗。
