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

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

doi:10.1039/d1bm00419k

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

Journal Article · Wed May 26 00:00:00 EDT 2021 · Biomaterials Science

DOI:https://doi.org/10.1039/d1bm00419k· OSTI ID:1813062

^[1]; Kim, Seok-Jo ^[2]; Cheresh, Paul ^[3]; Yun, Jeanho ^[4]; Lee, Byeongdu ^[5]; Kamp, David W. ^[3]; ^[6]

Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine; The Catholic Univ. of Korea, Bucheon (South Korea)
Jesse Brown VA Medical Center, Chicago, IL (United States); Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine; Univ. of Michigan, Ann Arbor, MI (United States)
Jesse Brown VA Medical Center, Chicago, IL (United States); Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine
Dong–A Univ., Busan (South Korea)
Argonne National Lab. (ANL), Argonne, IL (United States)
Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine; Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center; Northwestern Univ., Evanston, IL (United States)

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. Furthermore, 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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE; USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1813062

Alternate ID(s):: OSTI ID: 1821736
OSTI ID: 1785575

Journal Information:: Biomaterials Science, Journal Name: Biomaterials Science Journal Issue: 16 Vol. 9; ISSN 2047-4830

Publisher:: Royal Society of ChemistryCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
Mitochondrial targeting
cancer treatment
image-guided therapy
iron oxide nanoparticles
magnetic nano-transducers
mitochondrial dysfunction

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

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