M1 Macrophage‐Derived Extracellular Particles Induce Cell Death in MDA‐MB‐231 Cells

BACKGROUND: Triple-negative breast cancer (TNBC), a leading cause of female mortality worldwide, presents a treatment challenge due to the lack of targeted receptors. Macrophages, recognized for their role in the immune response, provide a promising avenue for cancer research. Given that macrophages secrete extracellular particles (EPs), which have been implicated in biological processes, including intercellular communication and immune modulation, it is hypothesized that EPs derived from macrophages could have potential anticancer effects. AIMS: This study examines the effect of M1 macrophage-secreted EPs on TNBC cells to investigate their potential as a therapeutic. METHODS AND RESULTS: Polarization was induced in RAW 264.7 macrophages and characterized using ELISA, nitrite release, and microscopy. Macrophage-derived EPs were isolated and characterized using nanoparticle tracking analysis, electron microscopy, and western blotting. The influence of EPs on MDA-MB-231 cells, a TNBC model, was assessed using confocal microscopy. Results showed the increasing expression of caspase 3/7 in a time-dependent manner (0, 24, and 48 h). Cell death was observed in TNBC cells with M1 macrophage-derived EPs, while cell proliferation was observed when M2 macrophage-derived EPs interacted with MDA-MB-231 cells. CONCLUSION: Overall, results showed that EPs derived from M1 macrophages could induce cell death in MDA-MB-321 cells, opening up potential options for new treatments in TNBC.