Interaction of targeted liposomes with primary cultured hepatic stellate cells: Involvement of multiple receptor systems
Interaction of targeted liposomes with primary cultured hepatic stellate cells: Involvement of multiple receptor systems
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DOI：
10.1016/j.jhep.2005.08.027
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发表时间：
2006-03-01
影响因子：
25.7
通讯作者：
Kamps, JAAM
中科院分区：
文献类型：
--
作者：
Adrian, JE;Poelstra, K;Kamps, JAAM
目的：研究甘露糖-6-磷酸甘露糖-人血清白蛋白(M6P-HSA)脂质体与培养细胞的相互作用。方法：将M6P-HSA共价偶联到脂质体表面，测定大鼠原代HSC和肝内皮细胞对~3H标记的M6P-HSA脂质体的摄取和结合。用免疫组织化学方法检测M6P-HSA脂质体对HSC的靶向性。结果：M6P-HSA脂质体与HSC的结合率是对照脂质体的4倍。过量的M6P-HSA抑制了58%的这种联系，表明M6P受体的特异性。清道夫受体竞争对手多肌苷酸取消了M6P-HSA脂质体与HSC的结合。M6P-HSA脂质体还与大量表达清道夫受体的内皮细胞结合。HSC对M6P-HSA脂质体的内吞作用具有温度依赖性，可被莫能菌素抑制。在肝纤维化模型中，M6P-HSA脂质体与HSC共定位。结论：M6P-HSA与脂质体的偶联可显著增加HSC和血管内皮细胞对M6P-HSA的体外摄取。甘露糖6-磷酸受体和清道夫受体都参与了摄取过程。M6P-HSA脂质体是肝纤维化肝星状细胞的潜在药物载体。(C)2005年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: In designing a versatile liposomal drug carrier to hepatic stellate cells (HSC), the interaction of mannose 6-phosphate human serum albumin (M6P-HSA) liposomes with cultured cells was studied.Methods: M6P-HSA was covalently coupled to the liposomal surface and the uptake and binding of 3H-labelled M6P-HSA liposomes by primary rat HSC and liver endothelial cells was determined. The targeting ability of M6P-HSA liposomes to HSC was tested in bile duct ligated rats using immunohistochemical methods.Results: The association of M6P-HSA liposomes with HSC was 4-fold higher than of control liposomes. An excess of M6P-HSA inhibited this association by 58%, indicating M6P receptor specificity. The scavenger receptor competitor polyinosinic acid abolished association of M6P-HSA liposomes with HSC. M6P-HSA liposomes also amply associated with endothelial cells, which abundantly express scavenger receptors. Endocytosis of M6P-HSA liposomes by HSC was temperature dependent and could be inhibited by monensin. In the fibrotic liver M6P-HSA liposomes co-localised with HSC.Conclusions: Coupling of M6P-HSA to liposomes strongly increases the in vitro uptake of these liposomes by HSC and endothelial cells. Both the mannose 6-phosphate receptor and the scavenger receptors are involved in the uptake process. M6P-HSA liposomes are potential drug carriers to HSC in the fibrotic liver. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.