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.

Efficient and High-Speed Transduction of an Antibody into Living Cells Using a Multifunctional Nanocarrier System to Control Intracellular Trafficking

“…b), probably because the ζ ‐potential likely reached a plateau when a certain amount of IgG became bound to the liposomal surface. Furthermore, a previous report showed that the cellular uptake of R8‐modified liposome itself was much higher than that of R8‐unmodified liposomes in the case of HeLa cells . On the basis of our results and findings of previous reports, it can be concluded that R8 assists both the loading of IgG on the liposomal surface and the cellular uptake of the carriers, thus resulting in the efficient cellular internalization of antibodies.…”

“…). We examined the effects of the following inhibitors: amiloride, a specific inhibitor of macropinocytosis by inhibiting the Na/H exchange required for macropinocytosis, a hypertonic medium containing sucrose to specifically inhibit clathrin‐mediated endocytosis through the dissociation of the clathrin lattice, and Fillipin III to specifically inhibit caveolar uptake via the depletion of cholesterol …”

“…We examined the effects of the following inhibitors: amiloride, a specific inhibitor of macropinocytosis by inhibiting the Na/H exchange required for macropinocytosis, a hypertonic medium containing sucrose to specifically inhibit clathrin-mediated endocytosis through the dissociation of the clathrin lattice, and Fillipin III to specifically inhibit caveolar uptake via the depletion of cholesterol. [35][36][37] As shown in Figure 8, the use of the macropinocytosis inhibitor (amiloride) or the clathrin-mediated endocytosis inhibitor (a hypertonic medium containing sucrose) largely inhibited the cellular uptake of R8-GALA-Lip-IgG, whereas no inhibition of cellular uptake was observed in the presence of the inhibitor of caveolar uptake (Fillipin III) (Fig. 8a).…”

Multidynamic Liposomes in Nanomedicine: Technology, Biology, Applications, and Disease Targeting

“…Thus, the β-MEND has the potential as an efficient nucleic acids delivering system targeted for efficient internalization in MIN6 for application in research and therapy based treatments of diabetes [72].…”

Antisense Cancer Therapy: Do Antisense Oligonucleotides Hold Promise as a Cure for Cancer?

“…The most common treatments for cancer are a) surgery, b) chemotherapy, c) radiation therapy, and d) targeted therapy. antisense therapeutic research [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Currently, over a hundred oligonucleotides are in clinical trials from 30 different pharmaceutical companies [23].…”