Homologous Fe3+/Al3+-Baicalin nanoplatform remodel the tumor microenvironment for triple-negative breast cancer via synergistic ferroptosis and immunogenic cell death

Triple-negative breast cancer (TNBC) is highly aggressive and lacks specific targeted therapeutic targets. Its immunosuppressive “cold” tumor microenvironment severely limits the efficacy of conventional chemotherapy and immunotherapy, resulting in unsatisfactory clinical outcomes. To address the challenges, we developed a biomimetic nanoplatform (M@Ba-Fe/Al NPs) by coating Fe 3+ /Al 3+ -baicalin cores with homologous tumor cell membranes. Benefiting from the inherent homologous targeting capability, the nanoplatform efficiently accumulates in tumor tissues and penetrates the dense cancer-associated fibroblast barrier to achieve deep tumor infiltration. Mechanistically, M@Ba-Fe/Al NPs induce tumor ferroptosis by triggering Fenton-like reactions to deplete intracellular glutathione and accelerate lipid peroxidation, while simultaneously activating immunogenic cell death (ICD). Additionally, Al 3+ acts as an immune adjuvant to promote dendritic cell maturation and increase intratumoral CD8 + T-cell infiltration, thereby comprehensively remodeling the immunosuppressive tumor microenvironment. By synergistically integrating ferroptosis and ICD dual antitumor pathways, the designed nanoplatform effectively suppresses tumor progression with favorable biosafety, providing a promising and translatable strategy for chemodynamic-immunotherapy of TNBC.