Metastasis is the predominant cause of
cancer deaths due to solid organ
malignancies; however, anticancer drugs are not effective in treating metastatic
cancer. Here we report a nanotherapeutic approach that combines magnetic nanocluster-based
hyperthermia and
free radical generation with an
immune checkpoint blockade (ICB) for effective suppression of both primary and secondary
tumors. We attached 2,2'-azobis(2-midinopropane) dihydrochloride (
AAPH) molecules to magnetic
iron oxide nanoclusters (IONCs) to form an IONC-
AAPH nanoplatform. The IONC can generate a high level of localized heat under an alternating magnetic field (AMF), which decomposes the
AAPH on the cluster surface and produces a large number of
carbon-centered
free radicals. A combination of localized heating and
free radicals can effectively kill
tumor cells under both normoxic and hypoxic conditions. The
tumor cell death caused by the combination of magnetic heating and
free radicals led to the release or exposure of various damage-associated molecule patterns, which promoted the maturation of dendritic cells. Treating the
tumor-bearing mice with IONC-
AAPH under AMF not only eradicated the
tumors but also generated systemic antitumor immune responses. The combination of IONC-
AAPH under AMF with anti-PD-1 ICB dramatically suppressed the growth of untreated distant
tumors and induced long-term immune memory. This IONC-
AAPH based magneto-
immunotherapy has the potential to effectively combat
metastasis and control
cancer recurrence.