Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong 226011, China.
Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai 200444, China.
ACS Appl Bio Mater. 2022 Jun 20;5(6):2481-2506. doi: 10.1021/acsabm.2c00199. Epub 2022 May 25.
Ferroptosis, characterized by iron-dependent lipid reactive oxygen species (ROS) accumulation, is non-apoptotic programmed cell death highly relevant to tumor development. It was found to manipulate oncogenes and resistant mutations of cancer cells via lipid metabolism pathways converging on phospholipid glutathione peroxidase (GPX4) that squanders lipid peroxides (L-OOH) to block the iron-mediated reactions of peroxides, thus rendering resistant cancer cells vulnerable to ferroptotic cell death. By accumulating ROS and lipid peroxidation (LPO) products to lethal levels in tumor microenvironment (TME), ferroptosis-driven nanotherapeutics show a superior ability of eradicating aggressive malignancies than traditional therapeutic modalities, especially for the drug-resistant tumors with high metastasis tendency. Moreover, Fenton reaction, inhibition of GPX-4, and exogenous regulation of LPO are three major therapeutic strategies to induce ferroptosis in cancer cells, which were generally applied in ferroptosis-driven nanotherapeutics. In this review, we elaborate current trends of ferroptosis-driven nanotherapeutics to reverse drug resistance of tumors in anticancer fields at the intersection of cancer biology, materials science, and chemistry. Finally, their challenges and perspectives toward feasible translational studies are spotlighted, which would ignite the hope of anti-resistant cancer treatment.
铁死亡是一种铁依赖性脂质活性氧（ROS）积累的细胞程序性死亡，与肿瘤的发生发展高度相关。它通过脂质代谢途径操纵癌基因和癌细胞的耐药突变，这些途径汇聚到磷脂谷胱甘肽过氧化物酶（GPX4）上，GPX4 会消耗脂质过氧化物（L-OOH），从而阻断过氧化物的铁介导反应，使耐药癌细胞容易发生铁死亡。通过在肿瘤微环境（TME）中积累 ROS 和脂质过氧化（LPO）产物至致死水平，铁死亡驱动的纳米疗法在根除侵袭性恶性肿瘤方面表现出比传统治疗方式更优越的能力，特别是对于具有高转移倾向的耐药肿瘤。此外，Fenton 反应、GPX-4 抑制和 LPO 的外源性调节是诱导癌细胞铁死亡的三种主要治疗策略，这些策略通常应用于铁死亡驱动的纳米疗法中。在这篇综述中，我们阐述了在癌症生物学、材料科学和化学的交叉领域中，铁死亡驱动的纳米疗法在抗癌领域中逆转肿瘤耐药性的最新趋势。最后，我们强调了它们向可行的转化研究的挑战和前景，这将为抗耐药性癌症治疗带来希望。
