TY - JOUR
T1 - Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth
AU - Kim, Sung Eun
AU - Zhang, Li
AU - Ma, Kai
AU - Riegman, Michelle
AU - Chen, Feng
AU - Ingold, Irina
AU - Conrad, Marcus
AU - Turker, Melik Ziya
AU - Gao, Minghui
AU - Jiang, Xuejun
AU - Monette, Sebastien
AU - Pauliah, Mohan
AU - Gonen, Mithat
AU - Zanzonico, Pat
AU - Quinn, Thomas
AU - Wiesner, Ulrich
AU - Bradbury, Michelle S.
AU - Overholtzer, Michael
N1 - 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.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84988735000&partnerID=8YFLogxK
U2 - 10.1038/nnano.2016.164
DO - 10.1038/nnano.2016.164
M3 - Article
C2 - 27668796
AN - SCOPUS:84988735000
SN - 1748-3387
VL - 11
SP - 977
EP - 985
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 11
ER -
