康奈尔大学(CORNELL UNIVERSITY)超细纳米颗粒诱导营养缺失的癌细胞发生铁死亡抑制肿瘤的生长

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

 

 

 

 

设计具有精确调谐物理化学特性的靶向肿瘤颗粒,可提高治疗时药物的输送和药物靶向性。然而,在分子层面上对推动纳米医学在生物系统中的命运的相互作用的理解仍然是难以理解的。

 

 

在这里,我们展示了超细(直径小于10纳米)聚乙二醇包覆的二氧化硅纳米颗粒,与黑色素靶向肽功能,可以诱导一种程序性细胞死亡的形式,即在饥饿的癌细胞和携带癌症的小鼠中称为的铁死亡。用大剂量的多重注射方案在静脉注射纳米颗粒的小鼠体内的肿瘤异种移植显示出生长或衰退的减少,这种结果被铁死亡的药物抑制剂liproxstatin-1逆转。这些数据表明,超细二氧化硅纳米颗粒可作为治疗铁死亡的靶点,具有一定的治疗潜力。

 

 

 

 

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

 

Abstract

The design of cancer-targeting particles with precisely tuned physicochemical properties may enhance the delivery of therapeutics and access to pharmacological targets. However, a molecular-level understanding of the interactions driving the fate of nanomedicine in biological systems remains elusive. Here, we show that ultrasmall (<10nm in diameter) poly(ethylene glycol)-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. Tumour 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.

 

Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth | Nature Nanotechnology  https://www.nature.com/articles/nnano.2016.164