Ferrimagnetic Vortex Nanorings-Mediated Mild Magnetic Hyperthermia Imparts Potent Immunological Effect for Treating Cancer Metastasis.

Cancer metastasis is a serious concern and a major reason of treatment failure. Herein, we have reported the development of an effective and safe nanotherapeutic strategy which can eradicate primary tumors, inhibit metastasizing to lung, and control the metastasis/growth of distant tumors. Briefly, ferrimagnetic vortex-domain iron oxide nanorings (FVIOs)-mediated mild magnetic hyperthermia caused calreticulin (CRT) expression on the 4T1 breast cancer cells. The CRT expression transmitted an "eat-me" signal and promoted phagocytic uptake of cancer cells by immune system to induce an efficient immunogenic cell death, further leading to the macrophages polarization. This mild thermotherapy promoted 88% increase of CD8+ cytotoxic T lymphocytes infiltration in distant tumors and triggered immunotherapy by effectively sensitizing tumors to the PD-L1 checkpoint blockade. The percentage of CD8+ cytotoxic T lymphocytes can be further increased from 55.4% to 64.5% after combining with PD-L1 blockade. Moreover, the combination treatment also inhibited the immunosuppressive response of anti-tumor, evidenced by significant down-regulation of myeloid-derived suppressor cells (MDSCs). Our results revealed that the FVIOs-mediated mild magnetic hyperthermia can activate the host immune systems and efficiently cooperate with PD-L1 blockade to inhibit the potential metastatic spreading as well as the growth of distant tumors.