The Effect of Cell Cluster Size on Intracellular Nanoparticle-Mediated Hyperthermia: Is It Possible to Treat Microscopic Tumors?

Abstract

Aim: To compare the measured surface temperature of variable size ensembles of cells heated by intracellular magnetic fluid hyperthermia with heat diffusion model predictions. Materials & methods: Starch-coated Bionized NanoFerrite (Micromod Partikeltechnologie GmbH, Rostock, Germany) iron oxide magnetic nanoparticles were loaded into cultured DU145 prostate cancer cells. Cell pellets of variable size were treated with alternating magnetic fields. The surface temperature of the pellets was measured in situ and the associated cytotoxicity was determined by clonogenic survival assay. Results & conclusion: For a given intracellular nanoparticle concentration, a critical minimum number of cells was required for cytotoxic hyperthermia. Above this threshold, cytotoxicity increased with increasing cell number. The measured surface temperatures were consistent with those predicted by a heat diffusion model that ignores intercellular thermal barriers. These results suggest a minimum tumor volume threshold of approximately 1 mm³, below which nanoparticle-mediated heating is unlikely to be effective as the sole cytotoxic agent.

Original submitted 31 October 2011; Revised submitted 29 February 2012; Published online 22 November 2012

Keywords::

• alternating magnetic field
• cancer therapy
• hyperthermia
• intracellular
• iron oxide
• magnetic nanoparticles

Disclaimer

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Financial & competing interests disclosure

C Gruettner and F Westphal are employees of micromod Partikeltechnologie, GmbH, manufacturer of the particles used in this study. This work was supported by an award from the Prostate Cancer Foundation/Safeway Foundation (STAR), and by Award Number U54CA143803 from the National Cancer Institute. Inductively coupled plasma mass spectrometry work was supported in part by the Maryland Cigarette Restitution Fund Program at Johns Hopkins Bloomberg School of Public Health and the NIEHS Center P30 ES00319. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgements

The authors thank M Delannoy at the Johns Hopkins School of Medicine Election Microscopy core facility (MD, USA) for help with transmission electron microscopy images.

Additional information

Funding

C Gruettner and F Westphal are employees of micromod Partikeltechnologie, GmbH, manufacturer of the particles used in this study. This work was supported by an award from the Prostate Cancer Foundation/Safeway Foundation (STAR), and by Award Number U54CA143803 from the National Cancer Institute. Inductively coupled plasma mass spectrometry work was supported in part by the Maryland Cigarette Restitution Fund Program at Johns Hopkins Bloomberg School of Public Health and the NIEHS Center P30 ES00319. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.