Effects of oligodeoxynucleotides on the physicochemical characteristics and cellular uptake of liposomes.

Effects of oligodeoxynucleotides on the physicochemical characteristics and cellular uptake of liposomes.
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寡脱氧核苷酸对脂质体理化特性和细胞摄取的影响。

DOI:
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发表时间:
1997
期刊:
Journal of Pharmacy and Science
影响因子:
--
通讯作者:
S. Tsuchiya
S. Tsuchiya
中科院分区:
--
文献类型:
--
作者:
H. Arima;Y. Aramaki;S. Tsuchiya

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我们研究了磷酸二酯寡脱氧核苷酸(ODN),这是在小鼠肿瘤坏死因子α基因(TNF-α)的AUG起始密码子附近的反义位点,对三种不同表面电荷的脂质体的理化特性和细胞缔合的影响。加入ODN后脂质体的理化性质发生了变化。当ODN/脂质摩尔比在阳离子(TMAG)脂质体[由N-(α-三甲基铵乙酰基)双十二烷基-D-谷氨酸盐氯化物(TMAG)、二月桂酰磷脂酰胆碱(DLPC)和二油酰磷脂酰乙醇胺(DOPE)以1:2:2的比例组成]中为约0.15时,但在中性和带负电荷的脂质体中不为约0.15时,脂质体聚集并融合。在较高的摩尔比下,TMA脂质体中的这些变化不明显。此外,在ODN/脂质摩尔比约为0.15时,ODN使TMAG脂质体的zeta电位从正变为负。因此,ODN诱导的聚集和融合可以通过TMAG脂质体之间较低的表面电荷排斥来解释。另一方面,ODN与小鼠巨噬细胞样细胞系RAW264.7细胞的相关性非常轻微。与中性和带负电荷的脂质体相比,通过包封在TMAG脂质体中,ODN的细胞结合显著增强。ODN加入到脂质体悬浮液中不影响TMAG脂质体细胞缔合的速率和程度,即使在ODN/脂质摩尔比约为0.15时也是如此。这些结果表明,脂质组成和ODN/脂质的摩尔比是关键的阳离子脂质体的理化特性。但这些变化对阳离子脂质体的细胞摄取特性影响较小。
We studied the effects of a phosphodiester oligodeoxynucleotide (ODN), which is antisense to the site in the neighborhood of the AUG initiation codon of the mouse tumor necrosis factor alpha gene (TNF-alpha), on the physicochemical characteristics and the cellular association of three types of liposomes with different surface charges. The physicochemical characteristics of the liposomes changed after adding ODN. When the ODN/lipid molar ratio was approximately 0.15 in cationic (TMAG) liposomes [consisting of N-(alpha-trimethylammonioacetyl)didodecyl-D-glutamate chloride (TMAG), dilauroylphosphatidylcholine (DLPC), and dioleolylphosphatidylethanolamine (DOPE) in a 1:2:2 ratio], but not in neutral and negatively charged liposomes, then the liposomes aggregated and fused. At higher molar ratios, these changes in TMA liposomes were not evident. In addition, ODN inverted the zeta-potential of TMAG liposomes from positive to negative at an ODN/lipid molar ratio of approximately 0.15. Therefore, the aggregation and fusion induced by ODN could be explained by a lower surface charge repulsion between TMAG liposomes. On the other hand, the association of ODN with RAW264.7 cells, a mouse macrophage-like cell line, was very slight. The cellular association of ODN was significantly enhanced compared with neutral and negatively charged liposomes by encapsulation in TMAG liposomes. The ODN added to liposome suspensions did not affect the rate and extent of TMAG liposome cellular association, even at an ODN/lipid molar ratio of approximately 0.15. These results indicate that the lipid composition and ODN/lipid molar ratio are critical for the physicochemical characteristics of cationic liposomes. However, the changes had less influence on the cellular uptake properties of cationic liposomes.
Lipofectin 增强细胞对反义 DNA 的摄取,同时抑制肿瘤细胞生长。
DOI: 10.1089/ard.1992.2.51
发表时间: 1992
期刊: Antisense research and development
影响因子: --
作者:
Yeoman,LC;Danels,YJ;Lynch,MJ
通讯作者: Lynch,MJ
DOI: 10.1016/0005-2736(92)90086-2
发表时间: 1992-01-31
期刊: BIOCHIMICA ET BIOPHYSICA ACTA
影响因子: --
作者:
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通讯作者: PAPAHADJOPOULOS, D
DOI: 10.1021/bi00517a023
发表时间: 1981-01-01
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
STRUCK, DK;HOEKSTRA, D;PAGANO, RE
通讯作者: PAGANO, RE
DOI: 10.1021/bi00450a039
发表时间: 1989-11-28
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
WANG, CY;HUANG, L
通讯作者: HUANG, L
DOI: 10.1016/0006-291x(91)91366-k
发表时间: 1991-08-30
影响因子: 3.1
作者:
GAO, X;HUANG, L
通讯作者: HUANG, L