Gene delivery to adipocyte remains a major hurdle in developing nucleic acid-based therapies for metabolic disorders. Conventional transfection vehicle and vaccine-type lipid nanoparticles (LNPs) show limited efficacy in these cells. To overcome this, we developed cubic phase LNPs using glycerol monooleate (GMO). Structural analysis by small-angle X-ray scattering and cryo-EM imaging confirmed a cubic internal organization, which is reported to be favorable for cellular uptake and endosomal escape. Flow cytometry reveled that GMO-based cubic phase LNPs achieve enhanced delivery efficiency compared to transfection reagent and conventional vaccine-type LNPs. These results suggest that the unique nanostructure of cubic phase LNPs improves uptake and gene delivery in adipocytes, highlighting their potential as a platform for adipocyte-targeted nucleic acid delivery.
Ko et al. (Sun,) studied this question.