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

• Published in: Journal of industrial and engineering chemistry (Seoul, Korea) Vol. 97; pp. 476 - 484
• Main Authors: Uthaman, Saji, Pillarisetti, Shameer, Huh, Kang Moo, Cho, Chong-Su, Park, In-Kyu
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 25.05.2021; 한국공업화학회
• Subjects: Antitumor immunity; Chemo-photothermal therapy; Immunological cell death; Metastasis; Nanoparticles; 화학공학; Nanoparticles; Antitumor immunity; Immunological cell death; Metastasis; Chemo-photothermal therapy
• ISSN: 1226-086X; 1876-794X
• DOI: 10.1016/j.jiec.2021.03.003

[Display omitted] 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.