Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth.
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.
Cell Biology Program, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.|BCMB Allied Program, Weill Cornell Medical College, New York, New York 10065, USA.
Sung Eun
SE
Kim
Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.
Li
L
Zhang
Department of Materials Science &Engineering, Cornell University, Ithaca, New York 14853, USA.
Kai
K
Ma
Cell Biology Program, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.
Michelle
M
Riegman
Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.
Feng
F
Chen
Helmholtz Zentrum München, Institute of Developmental Genetics, 85764 Neuherberg, Germany.
Irina
I
Ingold
Helmholtz Zentrum München, Institute of Developmental Genetics, 85764 Neuherberg, Germany.
Marcus
M
Conrad
Department of Materials Science &Engineering, Cornell University, Ithaca, New York 14853, USA.
Melik Ziya
MZ
Turker
Cell Biology Program, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.
Minghui
M
Gao
Cell Biology Program, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.|BCMB Allied Program, Weill Cornell Medical College, New York, New York 10065, USA.
Xuejun
X
Jiang
Tri-Institutional Laboratory of Comparative Pathology, The Rockefeller University, Sloan Kettering Institute for Cancer Research, Weill Cornell Medical College, New York, New York 10065, USA.
Sebastien
S
Monette
Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.
Mohan
M
Pauliah
Department of Epidemiology and Biostatistics, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.
Mithat
M
Gonen
Department of Medical Physics, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.
Pat
P
Zanzonico
Department of Biochemistry, University of Missouri, Columbia, Missouri 65211, USA.
Thomas
T
Quinn
Department of Materials Science &Engineering, Cornell University, Ithaca, New York 14853, USA.
Ulrich
U
Wiesner
Department of Radiology, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.|Molecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.
Michelle S
MS
Bradbury
Cell Biology Program, Sloan Kettering Institute for Cancer Research, New York, New York 10065, USA.|BCMB Allied Program, Weill Cornell Medical College, New York, New York 10065, USA.
Michael
M
Overholtzer
D000596:Amino Acids / Q000172:deficiency; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects; D008545:Melanoma; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011810:Quinoxalines / Q000494:pharmacology; D012822:Silicon Dioxide / Q000737:chemistry; D013141:Spiro Compounds / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D000521:alpha-MSH / Q000737:chemistry
D000596:Amino Acids; D000970:Antineoplastic Agents; D011810:Quinoxalines; D013141:Spiro Compounds; C000595890:liproxstatin-1; D011092:Polyethylene Glycols; D000521:alpha-MSH; D012822:Silicon Dioxide; D007501:Iron
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