Enhanced transfection efficiency into macrophages and dendritic cells by a combination method using mannosylated lipoplexes and bubble liposomes with ultrasound exposure.
To achieve effective gene therapy, it is necessary to selectively and efficiently transfect therapeutic gene into targeted cells. In this study, we developed a combination method using mannosylated lipoplexes, which show selectivity to antigen-presenting cells such as macrophages and dendritic cells, and bubble liposomes (BLs), which are known to enhance transfection efficiency on exposure to ultrasound (US). In cultured mouse macrophages, known for the expression of mannose receptors, the transfection efficiency of this combination method using mannosylated lipoplexes and BLs with US was higher than that of naked pDNA or unmodified lipoplexes and BLs. In the liver and spleen, the in vivo transfection efficiency of this combination method was significantly higher than that of naked pDNA or unmodified lipoplexes and BLs with US. Transfection in hepatic nonparenchymal cells using this combination method was about 12 times higher than that in hepatic parenchymal cells. As far as splenic transfection activities were concerned, the transfection efficiency of this combination method in CD11c(+) cells was significantly higher than that in CD11c(-) cells. In conclusion, we demonstrated that the gene transfection efficiency in macrophages and dendritic cells was significantly increased by this combination method using mannosylated lipoplexes and BLs with US exposure.
Un
Keita
K
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto 606-8501, Japan.
Kawakami
Shigeru
S
Suzuki
Ryo
R
Maruyama
Kazuo
K
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D007275:Injections, Intravenous; D042541:Intracellular Space / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism*; D051379:Mice; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000000981:diagnostic imaging; D013997:Time Factors; D014162:Transfection / Q000379:methods*; D014465:Ultrasonics; D014463:Ultrasonography
D008081:Liposomes; D012333:RNA, Messenger; D008156:Luciferases; D008358:Mannose