Latest advances in nanodrug delivery systems for modulating the immune microenvironment in triple-negative breast...

The tumor immune microenvironment (TIME), composed of tumor cells, immune/stromal cells, cytokines, and other components, plays a central role in determining tumor immunogenicity and response to therapy. The balance between effector T/NK cells and immunosuppressive populations such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and M2-like tumor-associated macrophages (TAMs) determines whether tumors remain "cold" or become "hot". Triple-negative breast cancer (TNBC) remains challenging to treat because it lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) targets and exhibits high heterogeneity. To address these limitations, tumor microenvironment (TME)-targeted nanocarriers have emerged as a promising strategy. By exploiting features such as hypoxia, acidity, redox imbalance, and abnormal vascular and mechanical cues, these systems enable prolonged circulation, active targeting, and stimulus-responsive release, thereby enhancing the efficacy of therapies such as immune checkpoint blockade. This review summarizes major nanoplatforms and therapeutic strategies, while highlighting translational barriers including TIME heterogeneity, enhanced permeability and retention (EPR) effect, and protein corona formation. Finally, this review explains why patient stratification should be incorporated into the future development of TNBC nano-immunotherapy and argues for simplified, reproducible nanocarrier designs to support clinically applicable precision treatment.