Co-Delivery Evodiamine-Porphyrin Nano-Drug to Enhance Photodynamic-Chemo-Immunotherapy for Triple-Negative Breast Cancer Treatment.

Abstract

Immunotherapy is a promising treatment for triple-negative breast cancer (TNBC), but the immunosuppressive tumor microenvironment (TME) compromises its efficacy. Therefore, the nano-drug TPGS@EVO/Ppa (TEP) is designed and prepared to achieve chemotherapy and enhance immunotherapy. Evodiamine (EVO) demonstrates chemotherapeutic efficacy and enhanced CD8⁺ T cell infiltration within the TME. Additionally, laser irradiation of Pyropheophorbide-a (Ppa) generates singlet oxygen, promoting tumor cell apoptosis and inducing immunogenic cell death (ICD). In vitro and in vivo experiments demonstrate that TEP exhibits significant cytotoxicity against 4T1 tumor cells and markedly inhibits tumor growth. Furthermore, TEP promotes the release of damage-associated molecular patterns (DAMPs) such as calreticulin (CRT), high mobility group box 1 protein (HMGB1), and adenosine triphosphate (ATP), which stimulates dendritic cells (DCs) maturation and activate adaptive immunity. Bilateral tumor experiments reveal that the combination therapy significantly increases the proportions of CD4⁺ and CD8⁺ T cells in tumors and central memory T cells (TCMs) in the spleen, demonstrating potent immunotherapy efficacy. In summary, TEP emerges as an innovative nano-drug with exceptional anti-tumor properties, offering a novel strategy for the treatment of TNBC.