Evaluation of inflammatory responses due to small interfering RNA transfer using unmodified- and mannose-modified bubble lipoplexes with ultrasound exposure in primary cultured macrophages.
Development of an efficient small interfering RNA (siRNA) delivery method using non-viral carriers is necessary to determine potent therapeutic effects of RNA interference. Inflammatory responses induced by siRNA interaction with Toll-like receptors and retinoic-acid-inducible gene I protein/melanoma differentiation-associated gene 5 (RIG-I/MDA-5) are obstacles to the application of siRNAs in clinically. Here, we evaluated the effects on inflammatory responses by our siRNA delivery method using bubble lipoplexes with ultrasound (US) exposure in cultured macrophages. The effective gene suppression effects were obtained under low-toxic conditions in this siRNA transfer method. The interferon (IFN)-α after siRNA transfer using lipoplexes/bubble lipoplexes with US exposure was not detected. However, low levels of type I IFN mRNA production were induced through interaction of siRNA and cytoplasmic RIG-I/MDA-5, but not Toll-like receptors. Our findings indicate that it is possible to develop a safe and efficient siRNA delivery technique using mannosylated bubble lipoplexes and US exposure.
['Yoshida|Mitsuru|M|', 'Kawakami|Shigeru|S|', 'Un|Keita|K|', 'Kono|Yusuke|Y|', 'Higuchi|Yuriko|Y|', 'Yamashita|Fumiyoshi|F|', 'Hashida|Mitsuru|M|']
D000818:Animals D002478:Cells, Cultured D053487:DEAD-box RNA Helicases D005260:Female D005786:Gene Expression Regulation D007249:Inflammation D000072640:Interferon-Induced Helicase, IFIH1 D016898:Interferon-alpha D008081:Liposomes D017737:Macrophages, Peritoneal D008358:Mannose D008565:Membrane Proteins D051379:Mice D008813:Mice, Inbred ICR D009419:Nerve Tissue Proteins D012333:RNA, Messenger D034741:RNA, Small Interfering D053633:Receptor, Interferon alpha-beta D011956:Receptors, Cell Surface D015398:Signal Transduction D051196:Toll-Like Receptor 3 D014162:Transfection D014465:Ultrasonics
ultrasound siRNA Drug delivery liposomes targeting