BSA-curcumin nanoparticles selectively target breast cancer cells and reprogram the immunosuppressive tumor...

Curcumin has potent anticancer properties but poor bioavailability. Nanoparticle delivery systems, particularly those based on albumin, offer a promising strategy to overcome this limitation. We developed bovine serum albumin-curcumin nanoparticles (BC-NPs) to enhance curcumin delivery and investigate their selective cytotoxicity and immunomodulatory effects in breast cancer.BC-NPs were synthesized via desolvation and characterized (FTIR, DLS, SEM). We assessed cytotoxicity (MTT assay), apoptosis (Annexin V/PI), and migration (wound healing) in MCF-7 (cancer) and MCF-10 A (normal) breast cell lines. We co-cultured treated cells with peripheral blood mononuclear cells (PBMCs) to evaluate effects on PBMC cell cycle and cytokine secretion (IFN-γ, TGF-β, IL-10) via flow cytometry and ELISA. Antioxidant status (TAC, GPx, MDA) and VEGF levels were also measured. BC-NPs exhibited a size of 133 ± 7 nm, a zeta potential of -43.9 mV, and high encapsulation efficiency (76.7%). Specifically, BC-NPs achieved an IC₅₀ of 14.53 µM in MCF-7 cells at 48 h - approximately half that of free curcumin (27.81 µM) - while maintaining significantly higher IC₅₀ values in normal MCF-10 A cells (195 µM), demonstrating a favorable therapeutic index. BC-NPs induced 44.0 ± 2.14% apoptosis in MCF-7 cells versus 8.42 ± 1.9% for free curcumin at the same concentration. At the immunological level, BC-NP treatment in the MCF-7 co-culture model significantly reduced TGF-β (p-value = 0.0007) and IL-10 (p-value = 0.01) while increasing IFN-γ production (p-value = 0.001), collectively remodeling the tumor microenvironment toward an antitumor immune phenotype. In co-culture, BC-NPs induced G0/G1 arrest in PBMCs and fostered an antitumor immune profile: decreasing immunosuppressive cytokines (TGF-β, IL-10) and increasing IFN-γ production. BC-NPs significantly enhance the therapeutic profile of curcumin by improving its bioavailability and conferring selective toxicity against breast cancer cells. Taken together, these data provide strong preclinical rationale for advancing BC-NPs into in vivo efficacy and safety studies, with particular attention to optimizing biodistribution and evaluating synergy with immune checkpoint inhibitors.