Zeitschrift für klinische und zelluläre Immunologie
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Macrophage Polarization and the Effect of MicroRNA-155 Administered in Water-in-Oil-in-Water Multiple Emulsion Formulations

Adwait Oka, Meghna Talekar, Qijun Ouyang, Ed Luther and Mansoor Amiji

The tumor microenvironment is composed of range of cells including macrophages that participate in sustaining tumor growth and invasion. Tumor-associated macrophages (TAM’s) polarized to the M2 or pro-tumoral phenotype are one such population of cells highly expressed in the tumor microenvironment. The expression of microRNA’s (miR’s) is often found to be dysregulated in TAM’s and hence exogenous delivery of miR provides a strategy for macrophage phenotypic modulation to attain improved anticancer activity. In this study, we assessed the use of multiple emulsions for the delivery of miR to achieve macrophage M1 repolarization. Water-in-oil-in-water (WOW) multiple emulsions (ME) were prepared using a two-step emulsification technique for encapsulation of miR-155 and cellular uptake, transfection efficiency, and repolarization capability of J774A.1 macrophages was assessed. The repolarized macrophages were co-cultured with SKOV3 ovarian cancer cells to assess the effect on macrophage morphology, motility and apoptosis of cancer cells. The ME showed enhanced uptake and expression of miR-155, which resulted in improved M1 polarization of J774A.1 cells. Co-culture studies with SKOV3 cells indicated an alteration in apoptotic profile. Holographic assessment of the co-cultured cells in real-time showed differences in motility and morphology of macrophages with miR-155 ME treated cells showing greater cellular interaction between the two phenotypes.