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

doi:10.1038/nnano.2016.164

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 journal › Article › peer-review

511 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 language	English
Pages (from-to)	977-985
Number of pages	9
Journal	Nature Nanotechnology
Volume	11
Issue number	11
DOIs	https://doi.org/10.1038/nnano.2016.164
Publication status	Published - 2016 Nov 1
Externally published	Yes

Bibliographical note

Funding Information:
This study was funded by grants from the National Institutes of Health (R01GM111350 to M.O.; 1R01CA161280-01A1 to M.B. and U.W.; 1U54 CA199081-01 to M.B. and U.W.; R01GM113013 and R01CA166413 to X.J.; Sloan Kettering Institute Core Grant P30 CA008748CCSG and the Benjamin Friedman Research Fund to M.O.). Peptide synthesis was conducted by the University of Missouri Structural Biology Core.

ASJC Scopus subject areas

Bioengineering
Atomic and Molecular Physics, and Optics
Biomedical Engineering
General Materials Science
Condensed Matter Physics
Electrical and Electronic Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nnano.2016.164

Cite this

Kim, S. E., Zhang, L., Ma, K., Riegman, M., Chen, F., Ingold, I., Conrad, M., Turker, M. Z., Gao, M., Jiang, X., Monette, S., Pauliah, M., Gonen, M., Zanzonico, P., Quinn, T., Wiesner, U., Bradbury, M. S., & Overholtzer, M. (2016). Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth. Nature Nanotechnology, 11(11), 977-985. https://doi.org/10.1038/nnano.2016.164

Kim, SE, Zhang, L, Ma, K, Riegman, M, Chen, F, Ingold, I, Conrad, M, Turker, MZ, Gao, M, Jiang, X, Monette, S, Pauliah, M, Gonen, M, Zanzonico, P, Quinn, T, Wiesner, U, Bradbury, MS & Overholtzer, M 2016, 'Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth', Nature Nanotechnology, vol. 11, no. 11, pp. 977-985. https://doi.org/10.1038/nnano.2016.164

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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.",

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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