TY - JOUR
T1 - A nanocarrier system for the delivery of nucleic acids targeted to a pancreatic beta cell line
AU - Yamada, Yuma
AU - Tabata, Mai
AU - Yasuzaki, Yukari
AU - Nomura, Masatoshi
AU - Shibata, Atsushi
AU - Ibayashi, Yuta
AU - Taniguchi, Yosuke
AU - Sasaki, Shigeki
AU - Harashima, Hideyoshi
N1 - Funding Information:
This work was supported, in part by, the Program for Promotion of Fundamental Studies in Health Sciences (project ID 10-62) of the National Institute of Biomedical Innovation, Japan (NIBIO) , a Grant-in-Aid for Scientific Research (S) (grant number 21229002 ) from the Ministry of Education, Culture, Sports, Science and Technology of Japanese Government (MEXT) . We thank Dr. J. Miyazaki for providing MIN6 cells. We also thank Dr. Milton Feather for his helpful advice in writing the manuscript.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.biomaterials.2014.04.017
DO - 10.1016/j.biomaterials.2014.04.017
M3 - Article
C2 - 24816283
AN - SCOPUS:84901428283
SN - 0142-9612
VL - 35
SP - 6430
EP - 6438
JO - Biomaterials
JF - Biomaterials
IS - 24
ER -
