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

Sung Eun Kim, Li Zhang, Kai Ma, Michelle Riegman, Feng Chen, Irina Ingold, Marcus Conrad, Melik Ziya Turker, Minghui Gao, Xuejun Jiang, Sebastien Monette, Mohan Pauliah, Mithat Gonen, Pat Zanzonico, Thomas Quinn, Ulrich Wiesner, Michelle S. Bradbury, Michael Overholtzer

Research output: Contribution to journalArticlepeer-review

274 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)977-985
Number of pages9
JournalNature Nanotechnology
Volume11
Issue number11
DOIs
Publication statusPublished - 2016 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrical and Electronic Engineering

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