Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth.

Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth.
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超质纳米颗粒会诱导养分缺乏的癌细胞中的铁毒性并抑制肿瘤的生长。

DOI:
10.1038/nnano.2016.164
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发表时间:
2016-11
影响因子:
38.3
通讯作者:
--
中科院分区:
材料科学1区
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--
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具有精确调整的物理化学特性的癌症靶向颗粒的设计可以增强治疗药物的递送和药理学靶点的获取。然而,分子水平上对生物系统中驱动纳米医学命运的相互作用的理解仍然难以捉摸。在这里,我们展示了超小(直径< 10纳米)聚乙二醇(PEG)包被二氧化硅纳米颗粒,用黑素瘤靶向肽功能化,可以诱导一种被称为铁凋亡的程序性细胞死亡形式在饥饿的癌细胞和癌小鼠中。使用高剂量多次注射方案静脉注射纳米颗粒的小鼠肿瘤异种移植物表现出生长或消退的减少,在某种程度上被铁下垂的药理学抑制剂利普司他汀-1逆转。这些数据表明,铁下垂可以靶向超小二氧化硅纳米颗粒,并可能具有治疗潜力。
The design of cancer-targeting particles with precisely-tuned physiocochemical properties may enhance delivery of therapeutics and access to pharmacological targets. However, molecular level understanding of the interactions driving the fate of nanomedicine in biological systems remains elusive. Here, we show that ultrasmall (< 10 nm in diameter) poly(ethylene glycol) (PEG)-coated silica nanoparticles, functionalized with melanoma-targeting peptides, can induce a form of programmed cell death known as ferroptosis in starved cancer cells and cancer-bearing mice. Tumor xenografts in mice intravenously injected with nanoparticles using a high-dose multiple injection scheme exhibit reduced growth or regression, in a manner that is reversed by the pharmacological inhibitor of ferroptosis, liproxstatin-1. These data demonstrate that ferroptosis can be targeted by ultrasmall silica nanoparticles and may have therapeutic potential.
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