Magneto mitochondrial dysfunction mediated cancer cell death using intracellular magnetic nano-transducers

Wooram Park, Seok Jo Kim, Paul Cheresh, Jeanho Yun, Byeongdu Lee, David W. Kamp, Dong Hyun Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Mitochondria are crucial regulators of the intrinsic pathway of cancer cell death. The high sensitivity of cancer cells to mitochondrial dysfunction offers opportunities for emerging targets in cancer therapy. Herein, magnetic nano-transducers, which convert external magnetic fields into physical stress, are designed to induce mitochondrial dysfunction to remotely kill cancer cells. Spindle-shaped iron oxide nanoparticles were synthesized to maximize cellular internalization and magnetic transduction. The magneto-mechanical transduction of nano-transducers in mitochondria enhances cancer cell apoptosis by promoting a mitochondrial quality control mechanism, referred to as mitophagy. In the liver cancer animal model, nano-transducers are infused into the local liver tumor via the hepatic artery. After treatment with a magnetic field, in vivo mitophagy-mediated cancer cell death was also confirmed by mitophagy markers, mitochondrial DNA damage assay, and TUNEL staining of tissues. This study is expected to contribute to the development of nanoparticle-mediated mitochondria-targeting cancer therapy and biological tools, such as magneto-genetics.

Original languageEnglish (US)
Pages (from-to)5497-5507
Number of pages11
JournalBiomaterials Science
Volume9
Issue number16
DOIs
StatePublished - Aug 21 2021

Funding

This work was mainly supported by grants R21CA173491, R01CA218659, and R01EB026207 from the National Cancer Institute and the National Institute of Biomedical Imaging and Bioengineering. This work was also supported by the Center for Translational Imaging and Mouse Histology and Phenotyping Laboratory at Northwestern University and the Basic Science Research Program (2021R1A2C4001776) through the National Research Foundation of Korea funded by the Ministry of Science and ICT (MSIT). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.

ASJC Scopus subject areas

  • Biomedical Engineering
  • General Materials Science

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