Abstract
Objective Deep-tissue localization of thermal doses is a long-standing challenge in magnetic field hyperthermia (MFH), and remains a limitation of the clinical application of MFH to date. Here, we show that pulse sequencing of MFH leads to a more persistent inhibition of tumor growth and less systemic impact than continuous MFH, even when delivering the same thermal dose. Methods We used an in vivo orthotopic murine model of pancreatic PANC-1 cancer, which was designed with a view to the forthcoming ‘NoCanTher’ clinical study, and featured MFH alongside systemic chemotherapy (SyC: gemcitabine and nab-paclitaxel). In parallel, in silico thermal modelling was implemented. Results Tumor volumes 27 days after the start of MFH/SyC treatment were 53% (of the initial volume) in the pulse MFH group, compared to 136% in the continuous MFH group, and 337% in the non-treated controls. Systemically, pulse MFH led to ca. 50% less core-temperature increase in the mice for a given injected dose of magnetic heating agent, and inflicted lower levels of the stress marker, as seen in the blood-borne neutrophil-to-lymphocyte ratio (1.7, compared to 3.2 for continuous MFH + SyC, and 1.2 for controls). Conclusion Our data provided insights into the influence of pulse sequencing on the observed biological outcomes, and validated the nature of the improved thermal dose localization, alongside significant lowering of the overall energy expenditure entailed in the treatment.
Highlights
Since it was first suggested by Gilchrist and colleagues in 1957 [1], magnetic field hyperthermia (MFH) has been explored as a cancer thermotherapy, using iron oxide magnetic nanoparticles (MNPs) as heating agents to deliver localized thermal energy into tumors (e.g [2,3].)
Impact of pulse or continuous MFH on orthotopic pancreatic tumors in mice On treating PANC-1-inoculated orthotopic pancreatic tumors in vivo with MFH combined with systemic chemotherapy (SyC), both pulse heating (Ps) and continuous heating (Cs) were effective in reducing tumor growth
Since pulse or continuous MFH as monotherapy attenuated the expression of stress and proliferation markers (i.e., Ki67 and HSP70), we suggest that SyC is the main driver of this effect
Summary
Since it was first suggested by Gilchrist and colleagues in 1957 [1], magnetic field hyperthermia (MFH) has been explored as a cancer thermotherapy, using iron oxide magnetic nanoparticles (MNPs) as heating agents to deliver localized thermal energy into tumors (e.g [2,3].). This energy is generated through magnetization reversal processes within the MNPs, driven by the presence of external time-varying magnetic fields (e.g [4,5].). The cytotoxic effects of hyperthermia can differ depending on the tumor cell phenotype [12]
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