Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells

Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracel...

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Bibliographic Details
Published in:Scientific reports 2018-09, Vol.8 (1), p.13210-12, Article 13210
Main Authors: Engelmann, Ulrich M., Roeth, Anjali A., Eberbeck, Dietmar, Buhl, Eva M., Neumann, Ulf P., Schmitz-Rode, Thomas, Slabu, Ioana
Format: Article
Language:English
Subjects:
13
631/61/2296
631/61/350/354
639/925/350/354
639/925/352/2733
639/925/928/1065
Cell death
Cytotoxicity
Fibroblasts
Heating
Humanities and Social Sciences
Hyperthermia
Intracellular
multidisciplinary
Nanoparticles
Pancreas
Pancreatic cancer
Science
Science (multidisciplinary)
Temperature effects
Temperature perception
Thermal energy
Tumor cells
Tumors
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Summary:Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95% was achieved by depositing an intracellular total thermal energy with about 50% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65% after MNP were internalized inside cells.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-31553-9