Magnetic hyperthermia using iron oxide nanoparticles via LDDS suppressed lymph node and lung metastasis in a mouse model.

Lymph node (LN) metastasis remains a critical determinant of cancer progression and prognosis, yet surgical interventions result in adverse effects. In this preclinical study, we investigated a minimally invasive therapeutic approach combining magnetic hyperthermia (MH) with a lymphatic drug delivery system (LDDS) using iron oxide nanoparticles (Resovist®). A custom-built MH device precisely regulated LN temperature at 45 °C. Using a mouse model (MXH10/Mo/lpr) of tumor-suspicious LN (ts-LN) metastasis, Resovist® was intranodally administered, followed by MH treatment. This combination significantly suppressed tumor growth in ts-LN and reduced lung metastasis, with enhanced M1 macrophage polarization and antitumor immune responses. Histopathology confirmed tumor necrosis and localized nanoparticle deposition, while qPCR of spleen tissue indicated differential immune modulation. No overt systemic toxicity was observed. The results demonstrated that this theranostic approach allows for real-time thermal control and effective regional tumor inhibition. The technique holds promise for early-stage cancer patients, offering a non-invasive, image-guided alternative to surgical LN resection with the potential for clinical translation.