Liposome-cell interactions in vitro: Effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes
Liposome-cell interactions in vitro: Effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes
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DOI：
10.1021/bi980096y
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发表时间：
1998-09-15
期刊：
影响因子：
2.9
通讯作者：
O'Brien, DF
中科院分区：
文献类型：
--
作者：
Miller, CR;Bondurant, B;O'Brien, DF
脂质体的细胞摄取通常被认为是通过脂质体吸附到细胞表面上和随后的内吞作用介导的。本报告检查了脂质体表面电荷对两种不同细胞系中脂质体结合和内吞作用的影响：人卵巢癌细胞系（HeLa）和鼠来源的单核巨噬细胞系（J774）。大单层脂质体由1，2-二油酰基-sn-甘油基-3-磷脂酰胆碱组成，加入或不加入带正电荷的脂质，1，2-二油酰基-3-二甲基铵丙二醇（DODAP），或带负电荷的脂质1，2-二油酰基-sn-甘油基-3-磷脂酰丝氨酸。在一些实验中，加入5摩尔%的阴离子PEG（2000）-PE或相同分子量的中性PEG脂质。发现HeLa细胞内吞带正电荷的脂质体的程度大于中性或带负电荷的脂质体。这种偏好不是脂质特异性的，因为包含阳离子花青染料DiIC 18-（3）以代替DODAP赋予正电荷导致类似程度的内吞作用。相反，阳离子和阴离子脂质体与J774细胞的脂质体相互作用的程度大于中性脂质体。用空间稳定脂质体（PEG脂质体）也观察到HeLa细胞对带正电荷的脂质体的更大摄取。虽然所有检查的PEG脂质体的内吞总量相对于常规脂质体减弱，但带正电荷的PEG脂质体的内吞程度最大，而带负电荷的PEG（2000）-PE脂质体几乎不被HeLa细胞内吞。将中性PEG脂质掺入脂质体中允许脂质体空间和静电效应以可允许与网状内皮系统的细胞的相互作用最小化的方式独立变化，但允许脂质体和增殖细胞之间的强相互作用。
The cellular uptake of liposomes is generally believed to be mediated by adsorption of liposomes onto the cell surface and subsequent endocytosis. This report examines the effect of liposome surface charge on liposomal binding and endocytosis in two different cell lines: a human ovarian carcinoma cell line (HeLa) and a murine derived mononuclear macrophage cell line (J774), The large unilamellar liposomes were composed of 1,2-dioleolyl-sn-glycero-3-phosphatidylcholine with and without the addition of either a positively charged lipid, 1,2-dioleoyl-3-dimethylammonium propanediol (DODAP), or a negatively charged lipid, 1,2-dioleolyl-sn-glycero-3-phosphatidylserine. In some experiments 5 mol% of the anionic PEG(2000)-PE or a neutral PEG lipid of the same molecular weight was added. HeLa cells were found to endocytose positively charged liposomes to a greater extent than either neutral or negatively charged liposomes. This preference was not lipid-specific since inclusion of a cationic cyanine dye, DiIC18- (3), to impart positive charge in place of DODAP resulted in a similar extent of endocytosis. In contrast the extent of liposome interaction with J774 cells was greater for both cationic and anionic liposomes than for neutral liposomes. The greater uptake of positively charged liposomes by HeLa cells was also observed with sterically stabilized liposomes (PEG liposomes). Although the overall amount of endocytosis for all the PEG liposomes examined was attenuated relative to conventional liposomes, the extent of endocytosis was greatest for positively charged PEG liposomes, whereas negatively charged PEG(2000)-PE liposomes were hardly endocytosed by the HeLa cells. Incorporation of a neutral PEG lipid into liposomes permits the independent variation of liposome steric and electrostatic effects in a manner that may allow interactions with cells of the reticuloendothelial system to be minimized, yet permit strong interactions between liposomes and proliferating cells.