Translating magnetic fluid hyperthermia toward lung cancer treatment

Magnetic fluid hyperthermia (MFH) emerges as a potential new therapeutic strategy for the treatment of lung cancer. However, the biological endpoints underpinning its therapeutic efficacy remain insufficiently defined in this tumor. In this work, we advance the translational potential of MFH by delineating metabolic, structural and biophysical endpoints in patient-derived lung cancer models. Specifically, we evaluated the effects of MFH using Mg_0.1-γ-Fe₂O₃(mPEG-silane)_0.5 nanoparticles (NPs) subjected to an alternating magnetic field (AMF) on patient-derived lung cancer cells (in vitro) and NUDE Balb/c mice bearing patient-derived lung cancer xenografts, PDX (in vivo). We elucidated that MFH induces metabolic dysfunction in lung cancer cells, leading to reduced proliferation, diminished colony formation and restricted cell migration. Moreover, alterations in metallomic profiles and changes in glycan structures were detected in lung cancer cells treated with MFH. These were accompanied by released matrix metalloproteinases (MMP-1, MMP-2, and MMP-9) and increased cell membrane permeability, indicating that the primary effect of MFH on human lung cancer cells targets membrane integrity and the cell-extracellular matrix environment. Studies have shown that mice bearing lung cancer PDX subjected to MFH experienced a significant reduction in tumor growth compared to the untreated control. The CEM43 value, representing the cumulative equivalent minutes at 43 °C, was estimated to be approximately 9.1 minutes in MFH-treated animals, while the specific absorption rate (SAR) ranged between 389 and 475 W g^-1. Together, these findings refine the characterization of hyperthermia treatment endpoints and demonstrate magnetic fluid hyperthermia as a promising translational approach for lung cancer therapy, meriting further evaluation in future clinical applications.