All‐In‐One Magnetic Nanoparticles for Thermo‐Immunotherapy of Malignant Melanoma

The poor immunogenicity and immunosuppressive microenvironment of malignant tumors pose considerable difficulties in cancer treatment. Herein, “all-in-one” magnetic nanoparticles (αPD-L1/CpG@MCL) are prepared for combining magnetic hyperthermia and immunotherapy with anti-PD-L1 antibodies and CpG. Magnetic hyperthermia using αPD-L1/CpG@MCL effectively eradicates malignant murine melanoma and induces antitumor immunity by improving the tumor microenvironment.

Abstract

Hyperthermia using magnetic nanoparticles is a promising cancer therapy that locally destroys tumors and induces antitumor immunity by releasing tumor antigens from dying cells. However, magnetic hyperthermia in malignant melanomas with poor immunogenicity and an immunosuppressive microenvironment remains challenging. Here, all-in-one magnetic nanoparticles (αPD-L1/CpG@MCL) are developed for thermo-immunotherapy that enables hyperthermia with magnetic nanoparticles and immunotherapy with anti-PD-L1 antibody and CpG to improve the immunosuppressive tumor microenvironment. Magnetic hyperthermia with magnetite cationic liposomes (MCL, without anti-PD-L1 antibody and CpG) inhibits tumor growth in B16F10 melanoma; however, complete tumor regression is not observed. In contrast, complete tumor regression is observed when mice are treated with thermo-immunotherapy using αPD-L1/CpG@MCL. Additionally, mice cured after magnetic hyperthermia with αPD-L1/CpG@MCL rejected rechallenge with B16F10 cells, and cytotoxicity assay using splenocytes from cured mice shows the induction of antitumor immunity against B16F10 cells. Analysis of tumor-infiltrating lymphocytes reveals that magnetic hyperthermia with αPD-L1/CpG@MCL increased CD8⁺ T lymphocytes and M1-like macrophages, and decreased M2-like macrophages, indicating an improvement in the tumor microenvironment. This study provides a key design strategy for all-in-one magnetic nanoparticles that could cure malignant melanomas.