A Novel Nanotechnology-Based Approach Against Triple-Negative Breast Cancer: Biocompatibility Assessment and Tumour-Associated Macrophage Repolarization Induced by HSA-MnO₂ Nanoparticles

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterised by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Its molecular profile makes traditional therapies less effective. Furthermore, TNBC is highly heterogeneous, with a complex immunosuppressive tumour microenvironment (TME). These factors highlight the need for new therapeutic strategies to be designed. The field of nanomedicine has led to several promising studies on nanoparticles used for cancer therapy. In this work, the effect of albumin-based nanoparticles functionalised with MnO2 (HSA-MnO2-NPs) and loaded with Fenretinide (FEN) and Salinomycin (SAL) against TNBC was evaluated. Specifically, the role of these nanoparticles in the therapeutic repolarization of tumour-associated macrophages (TAMs), from the pro-tumoral M2 phenotype to the pro-inflammatory M1 phenotype, was investigated in vitro. Biocompatibility assays were also performed to evaluate cytotoxicity and hemocompatibility. Ultimately, the results obtained in this study show an acceptable safety profile at therapeutically relevant concentrations and a promising effect of HSA-MnO2-NPs in the repolarization of TAMs toward a less immunosuppressive phenotype.