Abstract
<title>Abstract</title> <p> Tumor-associated macrophages (TAMs) predominantly exhibit an immunosuppressive M2 phenotype that promotes tumor progression. Reprogramming TAMs toward the pro-inflammatory M1 phenotype represents a promising strategy for cancer immunotherapy. This study developed targeted deoxycholic acid (DCA)-loaded nanoliposomes to enhance macrophage uptake and induce M2-to-M1 repolarization. <bold>Methods</bold> : DCA-loaded nanoliposomes were prepared by thin-film hydration and characterized using dynamic light scattering (DLS), zeta potential analysis, transmission electron microscopy (TEM), and high-performance liquid chromatography (HPLC). Cellular uptake was evaluated by fluorescence microscopy, cytotoxicity by the MTT assay, and macrophage polarization by flow cytometry using CD206 and CD80 as M2 and M1 markers, respectively. <bold>Results</bold> : The nanoliposomes exhibited a mean particle size of 158 nm, a polydispersity index of 0.28, a zeta potential of −12.8 mV, spherical morphology, and a high encapsulation efficiency of 82.94%. The formulation demonstrated concentration-dependent cytotoxicity with an IC₅₀ of 13.47 μM. Fluorescence microscopy confirmed enhanced intracellular uptake of targeted nanoliposomes. Flow cytometry revealed a significant decrease in CD206⁺ macrophages (76.8% to 21.7%) and an increase in CD80⁺ macrophages (18.6% to 68.3%), indicating efficient macrophage repolarization. <bold>Conclusions</bold> : Targeted DCA-loaded nanoliposomes exhibit favorable physicochemical properties, efficient intracellular delivery, and potent immunometabolic activity, effectively reprogramming macrophages from the M2 to the M1 phenotype. These findings support their potential as a macrophage-targeted nanotherapeutic platform for cancer immunotherapy. </p>