Enhanced antitumor effects of interferon-stimulating DNA and magnetic hyperthermia in a breast cancer rat model

This study examined the targeted delivery of interferon-stimulating DNA (ISD) by magnetic nanoparticles (MNPs) against breast cancer in a rat model. We synthesized Fe₃O₄ MNPs and modified their surface with silica and polyethyleneimine (Fe₃O₄@SiO₂@PEI) for biocompatibility and water dispersibility. A folic acid-linked polyethyleneimine (PEI-FA) was synthesized to enhance the targeted delivery of ISD to the breast cancer cells. The ISD-loaded Fe₃O₄@SiO₂@PEI MNPs at low concentrations significantly affected breast cancer cells by contributing to reduced oxidative stress, triggering a pathway to stimulate interferon-beta production. However, they did not affect non-tumorigenic MCF-10A cells. Furthermore, treating ISD-loaded MNPs significantly decreased the quantity of tumor cells in a rat model of breast cancer. Magnetic hyperthermia (MHT) improved the therapeutic efficacy by elevating the temperature of ISD-loaded MNPs over 40 °C under an alternating current magnetic field. In the rat model, there was an over 5-fold difference in tumor mass between the untreated groups and those treated with ISD and MHT. We observed that apoptosis, inflammation, and DNA damage markers were significantly changed in the tumor tissues of the rats. Despite the low amount of material (max 2 μg ISD) and short exposure to the magnetic field (1 h), the treatment results demonstrated encouraging outcomes.