Magnetically Activatable Solid Lipid Nanocomposites for Chemodynamic–Hyperthermia Combination Cancer Therapy

Abstract

Chemodynamic therapy (CDT) is a promising cancer treatment approach but insufficient endogenous H2O2 levels and off-target toxicity limit its efficacy. Here, we developed magnetically responsive nanocomposites coencapsulating Fe3O4 and CaO2 nanoparticles within solid lipid nanoparticles (SLNs) to enable on-demand generation of Fe2+ and H2O2in situ under alternating magnetic field (AMF) stimulation for enhanced CDT and precise spatiotemporal control. Under AMF, Fe3O4 nanoparticles generate localized heat that induces apoptosis in cancer cells and melts the SLNs, triggering Fe3O4 and CaO2 release to self-supply Fe2+ and H2O2. Field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) revealed nanosized particles with average diameters of 85.7 ± 18.1 nm and 82.0 ± 19.1 nm, respectively. The zeta potential was −46.3 mV, supporting colloidal stability. Fe3O4 and CaO2 loadings were 10.7 ± 2.0% and 60.3 ± 8.5%, respectively. Differential scanning calorimetry (DSC) showed a melting point of 46 °C, suitable for hyperthermia applications. Under AMF, Fe3O4–CaO2–SLNs increased the suspension temperature by ∼10 °C and induced strong reactive oxygen species (ROS) generation. In vitro tests with MG-63 human osteosarcoma cells showed high viability for nonactivated Fe3O4–CaO2–SLNs (82.9 ± 3.9% at 24 h), while AMF activation reduced viability to 6.1 ± 1.4%, consistent with triggered ROS production. Control Fe3O4–SLNs (without CaO2) induced lower cytotoxicity (58.3 ± 3.4%), confirming synergistic effects of hyperthermia and CDT. AMF-activated Fe3O4–CaO2–SLNs exhibited progressive viability reductions over time (38.0 ± 2.5% at 4 h, 19.8 ± 1.9% at 12 h, and 6.1 ± 1.4% at 24 h), indicating sustained H2O2/•OH generation by released CaO2/Fe3O4. Overall, nanoscale, magnetically activatable Fe3O4–CaO2–SLNs showed strong potential for on-demand synergistic CDT/hyperthermia treatment of solid tumors.