This study evaluated the potential of preformed, lyophilized, and ready-to-load lipid nanoparticles in transfecting primary cell cultures. Transfection efficiency and immunogenicity of lipid nanoparticles were assessed by monitoring the expression of GFP/mCherry mRNA cargo and by measuring cytokine levels using plate-based methods, respectively. Transfection of human monocyte-derived macrophages with SM-102 containing particles express GFP within 4 hours and peak by 16 hours with greater than 50% transfection efficiency.