Intracellular fate of octaarginine-modified liposomes in polarized MDCK cells
Intracellular fate of octaarginine-modified liposomes in polarized MDCK cells
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DOI：
10.1016/j.ijpharm.2009.11.005
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发表时间：
2010-02-15
影响因子：
5.8
通讯作者：
Harashima, Hideyoshi
中科院分区：
文献类型：
--
作者：
Fujiwara, Takahiro;Akita, Hidetaka;Harashima, Hideyoshi
八精氨酸(R8)修饰的脂质体可通过巨噬细胞吞噬有效的细胞摄取，被用于将治疗物质输送到细胞内。最近的分析表明，T8修饰的脂质体主要通过巨噬细胞吞噬作用被摄取。并有效地逃脱内体，以避免非极化NIH-3T3细胞的溶酶体降解。在本研究中，我们利用激光共聚焦扫描显微镜(CLSM)对R8修饰的脂质体在极化的MDCK细胞内的命运进行了评估，并与传统阳离子脂质体的转运进行了比较。与在NIH-3T3细胞中发生的情况相反，R8修饰的脂质体通过网状蛋白介导的内吞和巨噬细胞吞噬被MDCK细胞内化得同样好。在随后的MDCK细胞内转运中，最显著的特征是R8修饰的脂质体被困在内膜室，随后，它们中的一部分与高尔基体共定位。与高尔基仪器相似的共定位也观察到了辛氨酸(K8)修饰的脂质体。相反，阳离子脂质体被发现主要与溶酶体用溶酶追踪器染色共定位。总体而言，在极化的MDCK细胞中，阳离子多肽修饰的脂质体可能受到不同于阳离子脂类脂质体的分选途径。(C)2009爱思唯尔B.V.保留所有权利。
Octaarginine (R8)-modified liposomes have been used to deliver therapeutic substances into cells owing to the efficient cellular uptake via macropinocytosis. Recent analyses revealed that T8-modified liposomes are mainly taken up via macropinocytosis. and escape from endosomes efficiently to avoid lysosomal degradation in non-polarized NIH-3T3 cells. In the present study, we evaluated the intracellular fate of R8-modfied liposomes in polarized MDCK cells, comparing their trafficking with that of conventional cationic liposomes by confocal laser scanning microscopy (CLSM). In contrast to what occurs in NIH-3T3 cells, R8-modified liposomes are internalized by MDCK cells equally well via clathrin-mediated endocytosis and macropinocytosis. The most salient characteristic in subsequent intracellular trafficking in MDCK cells is that R8-modified liposomes become trapped in the endosomal compartment and subsequently, a portion of them colocalizes with the Golgi apparatus. Similar colocalization with the Golgi apparatus was observed for octalysine (K8)-modified liposomes. In contrast, cationic liposomes were found to colocalize predominantly with lysosomes stained with lysotracker. Collectively, in polarized MDCK cells, cationic peptide-modified liposomes may be subjected to a different sorting pathway from that used for liposomes composed of cationic lipids. (C) 2009 Elsevier B.V. All rights reserved.