A nanocarrier system for the delivery of nucleic acids targeted to a pancreatic beta cell line

Abstract

Pancreatic β cells secrete insulin in response to glucose levels and thus are involved in controlling blood glucose levels. A line of pancreatic β cells "MIN6" has been used in studies related to the function of β cells and diabetes therapy. Regulating gene expression in MIN6 cells could accelerate these studies, but an efficient method for the transfection of nucleic acids targeted to MIN6 cells is required. We report here on a liposome-based carrier targeted to pancreatic β cells (Multifunctional envelope-type nano device for pancreatic β cells, β-MEND). We identified a lipid composition for use in preparing the β-MEND, which permits the particles to be efficiently internalized into MIN6, as evidenced by flow cytometry analyses. Intracellular observation by confocal laser scanning microscopy showed that the β-MEND efficiently delivered the oligo nucleic acids to the cytosol of MIN6 cells. Moreover, using a β-MEND encapsulating a 2'-O-Methyl RNA complementary to a microRNA that suppresses insulin secretion, the knockdown of the targeted microRNA and an up-regulation of insulin secretion were observed in MIN6. Thus, the β-MEND holds promise as an efficient system for delivering nucleic acids targeted to MIN6 and can contribute to research and therapy aimed at diabetes.

Keywords: Diabetes; MIN6 cell; Multifunctional envelope-type nano device (MEND); Nucleic acids delivery; Pancreatic β cells; microRNA.