Monitoring Nanoparticle-Mediated Cellular Hyperthermia with A High-Sensitivity Biosensor

Abstract

Aim: To develop and apply a heat-responsive and secreted reporter assay for comparing cellular response to nanoparticle (NP)- and macroscopic-mediated sublethal hyperthermia. Materials & methods: Reporter cells were heated by water bath (macroscopic heating) or iron oxide NPs activated by alternating magnetic fields (nanoscopic heating). Cellular responses to these thermal stresses were measured in the conditioned media by secreted luciferase assay. Results & conclusion: Reporter activity was responsive to macroscopic and nanoparticle heating and activity correlated with measured macroscopic thermal dose. Significant cellular responses were observed with NP heating under doses that were insufficient to measurably change the temperature of the system. Under these conditions, the reporter response correlated with proximity to cells loaded with heated nanoparticles. These results suggest that NP and macroscopic hyperthermia may be distinctive under conditions of mild hyperthermia.

Keywords::

• heat shock
• hyperthermia
• iron oxide nanoparticle
• Metridia luciferase
• nanoparticle

Supplementary Material

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

Financial & competing interests disclosure

Funding for this project was supported by a grant from the Safeway Foundation and the Prostate Cancer Foundation (TL DeWeese and RH Getzenberg), a gift from the Mr. David Koch Foundation (SEL), and by Award Number U54CA143803 from the National Cancer Institute (R Ivkov). Inductively coupled plasma mass spectroscopy analysis was supported in part by the Maryland Cigarette Restitution Fund Program at the Johns Hopkins Bloomberg School of Public Health and the NIEHS Center P30E00319. 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 WH Chowdhury, D Coffey and L Chung for their valuable suggestions and critical discussions regarding this work. They also thank A Attaluri, M Seshadri and S Budri for their technical assistance.

Additional information

Funding

Funding for this project was supported by a grant from the Safeway Foundation and the Prostate Cancer Foundation (TL DeWeese and RH Getzenberg), a gift from the Mr. David Koch Foundation (SEL), and by Award Number U54CA143803 from the National Cancer Institute (R Ivkov). Inductively coupled plasma mass spectroscopy analysis was supported in part by the Maryland Cigarette Restitution Fund Program at the Johns Hopkins Bloomberg School of Public Health and the NIEHS Center P30E00319. 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.