Optimizing magnetic hyperthermia for melanoma: the role of nanoparticle uptake inhibition

Abstract Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used in magnetic hyperthermia, where their therapeutic efficacy depends on efficient heat generation. However, intracellular uptake of SPIONs has been shown to reduce their heat dissipation capacity, limiting hyperthermia performance. To address this challenge, we explored the use of small-molecule endocytosis inhibitors to block SPIONs’ uptake in vitro . SPIONs stabilized with 3-aminopropyl triethoxysilane (APTES) were evaluated in an advanced cutaneous melanoma cell line treated with a small library of endocytosis inhibitors. Among these, methyl- β -cyclodextrin significantly reduced SPIONs’ uptake compared to untreated cells. Importantly, uptake inhibition restored SPIONs’ heat dissipation capacity from specific absorption rates of 63 to 91 W g −1 and improved the temperature increase by 2.6 °C, under magnetic hyperthermia conditions. These findings demonstrate that targeting nanoparticle internalization with small-molecule inhibitors, particularly methyl- β -cyclodextrin, enhances the efficiency of magnetic hyperthermia in melanoma cells. This strategy offers a promising approach to optimize magnetic hyperthermia for melanoma treatment.