Capacitive-based radiofrequency (Rf) radiation at 27 MHz offers a non-invasive approach for inducing hyperthermia, making it a promising technique for thermal cancer therapy applications. To achieve focused and site-specific hyperthermia, external material is required that efficiently convert Rf radiation into localized heat. Nanomaterials capable of absorbing Rf energy and convert into heat for targeted ablation are of critical importance. In this study, we developed and evaluated an intra-tumoral injectable magnetic hydrogel (IT-MG) composed of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) impregnated in low molecular weight Hyaluronic Acid (HA) forming HA-SPIONs. Our systematic investigation revealed that HA-SPIONs exposed to Rf radiation produced significant temperature increases, reaching up to 50 °C. Further testing in tissue-mimicking phantom models showed consistent heating, with temperatures stabilizing at 43oC, ideal for localized hyperthermia. The ability of HA-SPIONs to act as an efficient localized heating agent when exposed to 27 MHz Rf radiation, reaching apoptosis-inducing temperature has not been previously reported. In conclusion, synergistic effects of IT-MG in both in-vitro and tumour mimicking phantom model demonstrates improved and localized hyperthermia facilitating adjuvant cancer treatment. 
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