Anthraquinone-Loaded Liposomes for TAM Reprogramming in Triple-Negative Breast Cancer: Mechanistic Rationale, Delivery Logic, and Translational Challenges

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited actionable targets, early recurrence, metastatic propensity, and variable responses to immune checkpoint blockade. Therapeutic resistance is closely associated with myeloid immunosuppression, in which tumor-associated macrophages (TAMs) promote T-cell exclusion, stromal remodeling, angiogenesis, metabolic dysfunction, and resistance to cytotoxic and immune-based therapies. Anthraquinone compounds, including emodin, aloe-emodin, rhein, and chrysophanol, may support TAM reprogramming by regulating tumor-cell stress responses, endoplasmic reticulum stress, immunogenic cell death-associated signaling, redox balance, immunometabolism, and STAT3/NF-κB-related inflammatory pathways. However, poor aqueous solubility, heterogeneous biodistribution, unstable systemic exposure, and potential off-target toxicity limit their translational development. Liposomal delivery offers a formulation strategy to improve solubilization, biodistribution, TAM-associated uptake/engagement, intracellular release, and therapeutic exposure windows. This review discusses anthraquinone-loaded liposomes for TAM reprogramming in TNBC by integrating mechanistic rationale, evidence boundaries, delivery logic, formulation determinants, and translational challenges, with particular attention to stress chaperone proteins, lipid composition, vesicle lamellarity, membrane phase state, responsive release, clinically relevant liposomal formulations, and clinical developability. Overall, anthraquinone-loaded liposomes are better positioned as immune microenvironment recalibration platforms or synergistic modulators in combination therapy rather than as standalone cytotoxic agents for TNBC.