화학공학소재연구정보센터
Journal of Industrial and Engineering Chemistry, Vol.97, 476-484, May, 2021
Drug-dye-apoptosis inducing micelles for enhancing host immunity against advanced metastatic breast cancer by the combination of low dose chemotherapy and photothermal therapy
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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-100 nm 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.
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