Su Yanhong, Liu Bing, Wang Binghan, Chan Leung, Xiong Chan, Lu Ligong, Zhang Xuanjun, Zhan Meixiao, He Weiling
Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, P. R. China.
Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.
Small. 2024 Jun;20(25):e2310342. doi: 10.1002/smll.202310342. Epub 2024 Jan 14.
Ferroptosis is a new form of regulated cell death featuring iron-dependent lipid peroxides accumulation to kill tumor cells. A growing body of evidence has shown the potential of ferroptosis-based cancer therapy in eradicating refractory malignancies that are resistant to apoptosis-based conventional therapies. In recent years, studies have reported a number of ferroptosis inducers that can increase the vulnerability of tumor cells to ferroptosis by regulating ferroptosis-related signaling pathways. Encouraged by the rapid development of ferroptosis-driven cancer therapies, interdisciplinary fields that combine ferroptosis, pharmaceutical chemistry, and nanotechnology are focused. First, the prerequisites and metabolic pathways for ferroptosis are briefly introduced. Then, in detail emerging ferroptosis inducers designed to boost ferroptosis-induced tumor therapy, including metal complexes, metal-based nanoparticles, and metal-free nanoparticles are summarized. Subsequently, the application of synergistic strategies that combine ferroptosis with apoptosis and other regulated cell death for cancer therapy, with emphasis on the use of both cuproptosis and ferroptosis to induce redox dysregulation in tumor and intracellular bimetallic copper/iron metabolism disorders during tumor treatment is discussed. Finally, challenges associated with clinical translation and potential future directions for potentiating cancer ferroptosis therapies are highlighted.
铁死亡是一种新的程序性细胞死亡形式，其特征是铁依赖性脂质过氧化物积累以杀死肿瘤细胞。越来越多的证据表明，基于铁死亡的癌症治疗在根除对基于凋亡的传统疗法耐药的难治性恶性肿瘤方面具有潜力。近年来，研究报道了许多铁死亡诱导剂，它们可以通过调节铁死亡相关信号通路来增加肿瘤细胞对铁死亡的易感性。受铁死亡驱动的癌症治疗快速发展的鼓舞，结合铁死亡、药物化学和纳米技术的跨学科领域受到关注。首先，简要介绍铁死亡的先决条件和代谢途径。然后，详细总结了旨在促进铁死亡诱导的肿瘤治疗的新型铁死亡诱导剂，包括金属配合物、金属基纳米颗粒和无金属纳米颗粒。随后，讨论了将铁死亡与凋亡和其他程序性细胞死亡相结合的协同策略在癌症治疗中的应用，重点是在肿瘤治疗期间利用铜死亡和铁死亡诱导肿瘤中的氧化还原失调和细胞内双金属铜/铁代谢紊乱。最后，强调了与临床转化相关的挑战以及增强癌症铁死亡治疗的潜在未来方向。
