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2017 ; 7
(6
): 1735-1748
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Elongated Nanoparticle Aggregates in Cancer Cells for Mechanical Destruction with
Low Frequency Rotating Magnetic Field
#MMPMID28529648
Shen Y
; Wu C
; Uyeda TQP
; Plaza GR
; Liu B
; Han Y
; Lesniak MS
; Cheng Y
Theranostics
2017[]; 7
(6
): 1735-1748
PMID28529648
show ga
Magnetic nanoparticles (MNPs) functionalized with targeting moieties can
recognize specific cell components and induce mechanical actuation under magnetic
field. Their size is adequate for reaching tumors and targeting cancer cells.
However, due to the nanometric size, the force generated by MNPs is smaller than
the force required for largely disrupting key components of cells. Here, we show
the magnetic assembly process of the nanoparticles inside the cells, to form
elongated aggregates with the size required to produce elevated mechanical
forces. We synthesized iron oxide nanoparticles doped with zinc, to obtain high
magnetization, and functionalized with the epidermal growth factor (EGF) peptide
for targeting cancer cells. Under a low frequency rotating magnetic field at 15
Hz and 40 mT, the internalized EGF-MNPs formed elongated aggregates and generated
hundreds of pN to dramatically damage the plasma and lysosomal membranes. The
physical disruption, including leakage of lysosomal hydrolases into the cytosol,
led to programmed cell death and necrosis. Our work provides a novel strategy of
designing magnetic nanomedicines for mechanical destruction of cancer cells.