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Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth
Open accessAbstract
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.
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“Two elegant studies have shown that the application of nanoparticles to tumor-bearing mice is sufficient to induce clinical remission.”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [112]
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“is potentially associated with a consistent release of immunostimulatory DAMPs [540, 541]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [541]
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“One of these papers implicated a direct tumoricidal effect of iron delivered by ultrasmall polyethylene glycol particles and attributed tumor regression to the induction of ferroptosis in malignant cells [112].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [112]
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Metadata
- Authors
- 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.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Cornell University (US)
- Helmholtz Munich (DE)
- University of Missouri (US)
- Corresponding author
- Bradbury, Michelle S.
- Overholtzer, Michael
- ORCID
- Venue
- Nature Nanotechnology
- Published
- 2016-09-26
- Volume
- 11
- Issue
- 11
- Pages
- 977-985
- ISSN
- 1748-3387 (ISSN-L)
- 1748-3395
- PMC
- PMC5108575
- OpenAlex
- W2527636586
- Cited by
- 622
- References
- 33
- Citations by year
- 2026: 27 · 2025: 52 · 2024: 72 · 2023: 67 · 2022: 89 · 2021: 83 · 2020: 85 · 2019: 56 · 2018: 49 · 2017: 38 · 2016: 2
- FWCI
- 43.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Nanotechnology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- National Institutes of Health (5u54ca199081-05)
- National Cancer Institute (R01CA161280, R01CA166413, U54-CA199081, P30CA008748)
- National Institute of General Medical Sciences (R01GM111350, R01GM113013)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- ferroptosis, ultrasmall nanoparticles, silica nanoparticles, polyethylene glycol coating, nutrient deprivation, cancer cell death, liproxstatin-1, tumor growth inhibition, nanomedicine, tumor xenografts, nanoparticle biodistribution
- MeSH terms
- alpha-MSH, Amino Acids, Animals, Antineoplastic Agents, Humans, Iron, Lysosomes, Melanoma, Particle Size, Polyethylene Glycols, Quinoxalines, Silicon Dioxide, Spiro Compounds, Mice, SCID, Cell Death, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, Nanoparticles
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