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Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth #MMPMID27668796
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
Nat Nanotechnol 2016[Nov]; 11 (11): 977-85 PMID27668796show ga
The design of cancer-targeting particles with precisely-tuned physiocochemical properties may enhance delivery of therapeutics and access to pharmacological targets. However, 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) (PEG)-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. Tumor 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.