引用本文:
Yasuya Kudo, Kazunori Koiwai, Kazuhiro Shimizu, Shota Kusuki, Mina Sakuragi, Naohiko Shimada, Yoichi Takeda, Kazuo Sakurai. Amidine-bearing lipoplex targeting to hepatocyte cells[J]. Chinese Chemical Letters,
2008, 19(9): 1115-1118.
doi:
10.1016/j.cclet.2008.06.001
Citation: Yasuya Kudo, Kazunori Koiwai, Kazuhiro Shimizu, Shota Kusuki, Mina Sakuragi, Naohiko Shimada, Yoichi Takeda, Kazuo Sakurai. Amidine-bearing lipoplex targeting to hepatocyte cells[J]. Chinese Chemical Letters, 2008, 19(9): 1115-1118. doi: 10.1016/j.cclet.2008.06.001
Citation: Yasuya Kudo, Kazunori Koiwai, Kazuhiro Shimizu, Shota Kusuki, Mina Sakuragi, Naohiko Shimada, Yoichi Takeda, Kazuo Sakurai. Amidine-bearing lipoplex targeting to hepatocyte cells[J]. Chinese Chemical Letters, 2008, 19(9): 1115-1118. doi: 10.1016/j.cclet.2008.06.001
Amidine-bearing lipoplex targeting to hepatocyte cells
摘要:
A lipoplex (i.e., pDNA#1/lipid complex and transfection reagent for pDNA delivery) containing galactosylceramide (GalCer) and an amidine-bearing lipid (TRX) was examined whether the bound pDNA was specifically ingested by hepatocyte via asialoglycoprotein receptor (ASGPR) and then expressed protein. Gel electrophoresis and small-angle X-ray scattering (SAXS) confirmed that the TRX-GalCer liposome#2 complexed with pDNA and the resultant lipoplex took a hexagonally packed inverted cylinder structure when the GalCer composition was less than 20 wt.% of the total lipid. When the lipoplex carrying pGL3 (luciferase-cording pDNA) was administrated to HepG2, the luciferase activity was increased with increasing the GalCer composition until it reached 3 wt.% and then decreased upon further addition of GalCer. When we added galactose itself as a competitor, the luciferase activity was decreased, while glucose did not show such decrease, suggesting that HepG2 ingested the lipoplex via ASGPR-mediated endocytosis. This paper indicated that the hexagonally packed inverted cylinder structures of lipoplex may not always provide excellent transfection and presented a possibility that the TRX lipoplex#3 can obtain a cellular-targeting ability through the receptors for oligosaccharide.
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关键词:
- Gene theraphy
- / Amidine
- / Galactosyleeramide
- / Targeting
English
Amidine-bearing lipoplex targeting to hepatocyte cells
Abstract:
A lipoplex (i.e., pDNA#1/lipid complex and transfection reagent for pDNA delivery) containing galactosylceramide (GalCer) and an amidine-bearing lipid (TRX) was examined whether the bound pDNA was specifically ingested by hepatocyte via asialoglycoprotein receptor (ASGPR) and then expressed protein. Gel electrophoresis and small-angle X-ray scattering (SAXS) confirmed that the TRX-GalCer liposome#2 complexed with pDNA and the resultant lipoplex took a hexagonally packed inverted cylinder structure when the GalCer composition was less than 20 wt.% of the total lipid. When the lipoplex carrying pGL3 (luciferase-cording pDNA) was administrated to HepG2, the luciferase activity was increased with increasing the GalCer composition until it reached 3 wt.% and then decreased upon further addition of GalCer. When we added galactose itself as a competitor, the luciferase activity was decreased, while glucose did not show such decrease, suggesting that HepG2 ingested the lipoplex via ASGPR-mediated endocytosis. This paper indicated that the hexagonally packed inverted cylinder structures of lipoplex may not always provide excellent transfection and presented a possibility that the TRX lipoplex#3 can obtain a cellular-targeting ability through the receptors for oligosaccharide.
-
Key words:
- Gene theraphy
- / Amidine
- / Galactosyleeramide
- / Targeting
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