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

Nat Nanotechnol. 2016 Nov;11(11):977-985. doi: 10.1038/nnano.2016.164. Epub 2016 Sep 26.


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 (<10 nm 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / deficiency
  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Humans
  • Iron / metabolism*
  • Lysosomes / drug effects
  • Melanoma
  • Mice
  • Mice, SCID
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Quinoxalines / pharmacology
  • Silicon Dioxide / chemistry
  • Spiro Compounds / pharmacology
  • Xenograft Model Antitumor Assays
  • alpha-MSH / chemistry


  • Amino Acids
  • Antineoplastic Agents
  • Quinoxalines
  • Spiro Compounds
  • liproxstatin-1
  • Polyethylene Glycols
  • alpha-MSH
  • Silicon Dioxide
  • Iron