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铁死亡的机制与治疗靶点:对纳米医学设计的启示

Mechanisms and therapeutic targets of ferroptosis: Implications for nanomedicine design.

作者信息

Zhang Meihong, Guo Mengqin, Gao Yue, Wu Chuanbin, Pan Xin, Huang Zhengwei

机构信息

College of Pharmacy, University of Jinan, Guangzhou, 510632, China.

College of Pharmacy, University of Sun Yat-sen, Guangzhou, 510275, China.

出版信息

J Pharm Anal. 2024 Jul;14(7):100960. doi: 10.1016/j.jpha.2024.03.001. Epub 2024 Mar 8.

DOI:10.1016/j.jpha.2024.03.001
PMID:39135963
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11318476/
Abstract

Ferroptosis is a nonapoptotic form of cell death and differs considerably from the well-known forms of cell death in terms of cell morphology, genetics, and biochemistry. The three primary pathways for cell ferroptosis are system Xc/glutathione peroxidase 4 (GPX4), lipid metabolism, and ferric metabolism. Since the discovery of ferroptosis, mounting evidence has revealed its critical regulatory role in several diseases, especially as a novel potential target for cancer therapy, thereby attracting increasing attention in the fields of tumor biology and anti-tumor therapy. Accordingly, broad prospects exist for identifying ferroptosis as a potential therapeutic target. In this review, we aimed to systematically summarize the activation and defense mechanisms of ferroptosis, highlight the therapeutic targets, and discuss the design of nanomedicines for ferroptosis regulation. In addition, we opted to present the advantages and disadvantages of current ferroptosis research and provide an optimistic vision of future directions in related fields. Overall, we aim to provide new ideas for further ferroptosis research and inspire new strategies for disease diagnosis and treatment.

摘要

铁死亡是一种非凋亡形式的细胞死亡,在细胞形态、遗传学和生物化学方面与众所周知的细胞死亡形式有很大不同。细胞铁死亡的三条主要途径是系统Xc/谷胱甘肽过氧化物酶4(GPX4)、脂质代谢和铁代谢。自铁死亡被发现以来,越来越多的证据揭示了其在多种疾病中的关键调节作用,尤其是作为癌症治疗的一个新的潜在靶点,从而在肿瘤生物学和抗肿瘤治疗领域引起了越来越多的关注。因此,将铁死亡确定为潜在治疗靶点具有广阔的前景。在这篇综述中,我们旨在系统地总结铁死亡的激活和防御机制,突出治疗靶点,并讨论用于调节铁死亡的纳米药物设计。此外,我们选择介绍当前铁死亡研究的优缺点,并对相关领域的未来方向提供乐观的展望。总体而言,我们旨在为进一步的铁死亡研究提供新思路,并激发疾病诊断和治疗的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/c9b78c0563ca/gr12.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/c9b78c0563ca/gr12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/12834657bca8/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/1f2816e3d937/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/f1e1ab5cf14d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/25bc0d56aa9b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/857b091dfc33/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/93d1b3f56cb1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/f4e12e081c1f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/56a9a9a067e0/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/2c6fb0fa5bd7/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/0dcc2dc097d0/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/f20dd5bf01bd/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/b5f52741cbff/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/553d/11318476/c9b78c0563ca/gr12.jpg

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Health Care Sci. 2022 Aug 9;1(2):93-110. doi: 10.1002/hcs2.5. eCollection 2022 Oct.
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Bioinformatics analysis and experimental validation reveal the anti-ferroptosis effect of FZD7 in acute kidney injury.生物信息学分析和实验验证揭示了FZD7在急性肾损伤中的抗铁死亡作用。
Biochem Biophys Res Commun. 2024 Jan 15;692:149359. doi: 10.1016/j.bbrc.2023.149359. Epub 2023 Dec 6.
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Ferroptosis-Mediated Immune Microenvironment and Therapeutic Response in Inflammatory Bowel Disease.
肺部疾病和肺癌中的铁死亡:分子机制、相互作用调节及治疗策略
MedComm (2020). 2025 Feb 23;6(3):e70116. doi: 10.1002/mco2.70116. eCollection 2025 Mar.
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Mechanisms of ferroptosis and targeted therapeutic approaches in urological malignancies.泌尿外科恶性肿瘤中铁死亡的机制及靶向治疗方法
Cell Death Discov. 2024 Oct 9;10(1):432. doi: 10.1038/s41420-024-02195-w.
铁死亡在炎症性肠病中的免疫微环境和治疗反应。
DNA Cell Biol. 2023 Dec;42(12):720-734. doi: 10.1089/dna.2023.0260. Epub 2023 Nov 10.
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