Rosmarinic acid/Se4+ self-assembled nanoparticles for combinational therapy of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) presents a formidable clinical challenge due to its aggressive nature and limited treatment options, with immunotherapy often hampered by the immunosuppressive "cold" tumor microenvironment. To address this, we developed a biomimetic nanoplatform (RA-Se@M) through the self-assembly of natural rosmarinic acid (RA) and selenium ions (Se4+), followed by coating with homologous cancer cell membranes. This design leverages the direct anti-tumor activity of RA and the immunomodulatory capacity of Se4+, while the membrane cloak confers immune evasion and enhanced tumor-targeting capability. The resulting RA-Se@M nanoparticles demonstrated superior homologous targeting and accumulation in 4T1 tumors in vivo. Beyond inducing potent apoptosis in cancer cells, RA-Se@M triggered robust immunogenic cell death (ICD), as evidenced by calreticulin exposure, HMGB1 release, and dendritic cell maturation. Consequently, in a syngeneic TNBC mouse model, RA-Se@M significantly suppressed tumor growth and, when combined with anti-PD-1 therapy, promoted profound intratumoral infiltration of cytotoxic T cells and achieved the most potent therapeutic outcome. The work showcases a promising biomimetic strategy that synergizes targeted chemotherapy and in situ immunotherapy to potentiate the anti-tumor immune response against TNBC.