Drug-dye-apoptosis inducing micelles for enhancing host immunity against advanced metastatic breast cancer by the combination of low dose chemotherapy and photothermal therapy

Abstract

Tumor metastasis is associated with high mortality in breast cancer patients. Although photothermal therapy (PTT) has arisen as a promising anticancer treatment approach, PTT-based monotherapies still fail to eradicate advanced cancers due to the immunosuppressive microenvironment. Herein, we synthesized drug-dye-lipid-like micelles composed of thermoresponsive poloxamer conjugated with linoleic acid (PCLA) loaded with a chemotherapeutic drug doxorubicin (DOX) and a near-infrared dye IR-780 (PCLA-ID) to enhance antitumor immunity against progressive metastatic breast cancers. Intravenous administration of sub-100nm sized PCLA-ID in breast tumor-bearing mice followed by local laser irradiation eliminated not only primary tumors, but also untreated distant tumors (abscopal effect). The combinatorial treatment of apoptosis-inducing PCLA-ID, which contained DOX at a subtherapeutic dose, and PTT augmented the maturation of tumor-draining lymph nodes, the upregulation of cytotoxic T lymphocytes, and the suppression of regulatory T cells in untreated secondary tumors. These events prevented lung metastasis in tumor-bearing mice after re-challenging with a second injection of breast cancer cells. We conclude that PCLA-ID nanoparticles can enhance immunogenic cell death, representing a promising strategy for triggering immune responses against advanced metastatic breast cancers.