Gene interfered-ferroptosis therapy for cancers.
Gene interfered-ferroptosis therapy for cancers.
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DOI：
10.1038/s41467-021-25632-1
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发表时间：
2021-09-07
影响因子：
16.6
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Gao J;Luo T;Wang J
虽然目前已有一些有效的治疗方法，但由于肿瘤的耐药性和患者的低反应性，仍然对人类的健康和生命构成了巨大的威胁。在这里，我们开发了一种基于铁沉积症的治疗方法，将纳米铁颗粒和癌症特异性基因干扰结合起来。癌细胞中两个铁代谢基因（FPN和LCN 2）的表达被Cas 13 a或由NF-κ B特异性启动子控制的microRNA选择性敲除。同时用铁纳米颗粒处理细胞。结果，在多种癌细胞中诱导了显着的铁细胞凋亡。然而，同样的处理对正常细胞的影响很小。通过腺相关病毒和纳米铁颗粒联合基因转移，在小鼠体内获得了显著的肿瘤生长抑制和持久的治愈。因此，在这项工作中，我们展示了一种基于基因干扰增强铁凋亡的癌症治疗方法。需要改进的治疗策略，因为耐药性限制了几种临床批准的癌症治疗剂的治疗功效。在这里，作者报告了一种基于铁中毒的治疗方法，使用铁纳米颗粒与基因干扰的组合来敲低铁代谢基因FPN和LCN 2。
Although some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we develop a ferroptosis-based therapy by combining iron nanoparticles and cancer-specific gene interference. The expression of two iron metabolic genes (FPN and LCN2) was selectively knocked down in cancer cells by Cas13a or microRNA controlled by a NF-κB-specific promoter. Cells were simultaneously treated by iron nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells. However, the same treatment had little effect on normal cells. By transferring genes with adeno-associated virus and iron nanoparticles, the significant tumor growth inhibition and durable cure were obtained in mice with the therapy. In this work, we thus show a cancer therapy based on gene interference-enhanced ferroptosis. Improved therapeutic strategies are needed as drug resistance limits the therapeutic efficacy of several clinically approved cancer therapeutics. Here, the authors report a ferroptosis-based therapy using a combination of iron nanoparticles with gene interference to knockdown iron metabolic genes, FPN and LCN2.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
2.5
作者：
Liu, Yingxun;Chen, Zhongping;Wang, Jinke
通讯作者：
Wang, Jinke
DOI：
10.1073/pnas.1415518111
发表时间：
2014-11-25
影响因子：
11.1
作者：
Linkermann, Andreas;Skouta, Rachid;Krautwald, Stefan
通讯作者：
Krautwald, Stefan
DOI：
10.1007/978-981-13-9589-5_2
发表时间：
2019-01-01
期刊：
BRAIN IRON METABOLISM AND CNS DISEASES
影响因子：
--
作者：
Gao, Guofen;Li, Jie;Chang, Yan-Zhong
通讯作者：
Chang, Yan-Zhong
影响因子：
4.1
作者：
Petrat, F;de Groot, H;Rauen, U
通讯作者：
Rauen, U