In Vivo Fluorescent Melanoma Model: Electroporation Plus Magnetic Hyperthermia Significatively Reduces Tumor Size,...

Background/Objectives: Melanoma affects both sexes, and its incidence has increased in recent years. It is currently among the most common types of cancer. Standard chemotherapy, although effective, often lacks selectivity for tumor cells, resulting in dose-limiting side effects. Electrochemotherapy and magnetic hyperthermia have been investigated as innovative biomedical approaches. Electrochemotherapy improves drug delivery by facilitating electroporation, thereby increasing intracellular concentrations of chemotherapeutic agents and reducing associated adverse effects. Furthermore, electroporation enhances sensitivity to magnetic hyperthermia. However, few studies have focused on the combination of electroporation and hyperthermia in melanoma models. This study aimed to evaluate the synergistic effects of intratumoral administration of superparamagnetic iron oxide nanoparticles (SPIONs), electroporation (EP), and magnetic hyperthermia (EHP) on fluorescent melanoma tumors generated with the MV3-GFP cell line. Methods: Fluorescent melanoma tumors were generated using the MV3-GFP cell line. Treatments included SPIONs alone, SPIONs combined with hyperthermia, and SPIONs combined with electroporation and hyperthermia. Tumor size was monitored over 21 and 28 days. Results: SPIONs alone did not affect tumor growth (665 mm³). SPIONs plus hyperthermia reduced tumor size to 126.5 mm³ at day 21. The combination of SPIONs, electroporation, and hyperthermia produced a pronounced antitumoral effect, with tumor size decreasing to 95.5 mm³ at day 14 and 6.8 mm³ at day 21, followed by complete tumor disappearance by day 28. Electroporation significantly enhanced the antitumoral activity of the combined treatment. Conclusions: The combination of SPIONs, electroporation, and magnetic hyperthermia shows significant synergistic antitumoral activity in a melanoma model. These findings support further investigation in larger and more comprehensive in vivo studies to better understand the therapeutic potential of these combined approaches.