Elongated Nanoparticle Aggregates in Cancer Cells for Mechanical Destruction with Low Frequency Rotating Magnetic Field

Theranostics
Yajing ShenYu Cheng

Abstract

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.

Citations

Aug 25, 2018·Electromagnetic Biology and Medicine·Meng ZhaXin Zhang
May 5, 2020·Frontiers in Bioengineering and Biotechnology·Abdel Rahman Abdel Fattah, Adrian Ranga
Jul 1, 2020·Advanced Science·Jiaojiao WuYu Cheng
Jul 31, 2019·Chemical Science·Arghya BandyopadhyaySayan Bhattacharyya
Jul 27, 2017·Annals of Biomedical Engineering·Yajing ShenGustavo R Plaza
Apr 3, 2019·Annual Review of Neuroscience·Michael G ChristiansenPolina Anikeeva
Sep 24, 2019·Future Medicinal Chemistry·Raul OrtizJose Prados
Mar 20, 2019·Pharmaceutics·Courtney van BallegooieDonald T Yapp
Dec 29, 2020·Frontiers in Bioengineering and Biotechnology·Henry Ruiz-GarciaDaniel M Trifiletti
Mar 20, 2021·ACS Applied Materials & Interfaces·Aleksey A NikitinMaxim A Abakumov
Jul 6, 2020·Journal of Colloid and Interface Science·Tanja GoršakDarko Makovec
Jul 19, 2017·ACS Applied Materials & Interfaces·Liuyang ZhangXianqiao Wang
Aug 31, 2021·Journal of Imaging·River GassenKathrin Spendier

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Methods Mentioned

BETA
Assay
protein assay
transmission electron microscopy
X-ray
confocal microscopy
flow cytometry
flow cytometery

Software Mentioned

FlowJo
Graphpad Prism
Image
GraphPad
Pro Plus

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