Potential of Magnetic Hyperthermia to Stimulate Localized Immune Activation

Thomas J. Carter, Giulia Agliardi, Fang Yu Lin, Matthew Ellis, Clare Jones, Mathew Robson, Angela Richard-Londt, Paul Southern, Mark Lythgoe, May Zaw Thin, Vyacheslav Ryzhov, Rafael T.M. de Rosales, Cordula Gruettner, Maha R.A. Abdollah, R. Barbara Pedley, Quentin A. Pankhurst, Tammy L. Kalber, Sebastian Brandner, Sergio Quezada, Paul MulhollandMaxim Shevtsov, Kerry Chester*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Magnetic hyperthermia (MH) harnesses the heat-releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium-89-positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21–87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat-shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti-tumor immune response.

Original languageEnglish
Article number2005241
JournalSmall
Volume17
Issue number14
Early online date18 Mar 2021
DOIs
Publication statusPublished - 8 Apr 2021

Keywords

  • biological response
  • heat-shock protein 70
  • immune stimulation
  • magnetic hyperthermia
  • superparamagnetic iron oxide nanoparticles

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