Characterization of CD44-mediated cancer cell uptake and intracellular distribution of hyaluronan-grafted liposomes.
Characterization of CD44-mediated cancer cell uptake and intracellular distribution of hyaluronan-grafted liposomes.
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DOI：
10.1021/mp2000428
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发表时间：
2011-08-01
影响因子：
4.9
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Qhattal HS;Liu X
透明质酸（HA）是一种生物相容性和可生物降解的线性多糖，通过细胞表面CD44受体靶向肿瘤。透明质酸与CD44受体高亲和力结合，CD44受体在许多肿瘤中过度表达并参与肿瘤转移。在本研究中，我们研究了HA分子量（MW）、接枝密度和CD44受体密度对HA接枝脂质体（HA-liposomes）被癌细胞内吞的影响。此外，还测定了ha脂质体的细胞内定位。不同分子量（5-8、10-12、175-350和1600 kDa）的ha以不同的接枝密度与脂质体结合。采用十六烷基三甲基溴化铵浊度法定量测定HA表面密度。流式细胞术和荧光显微镜观察ha脂质体的细胞摄取和亚细胞定位。HA-脂质体的平均粒径为120 ~ 180 nm，随HA的增大而增大。HA脂质体的摄取与HA分子量（5-8 < 10-12 < 175-350 kDa）、接枝密度和CD44受体密度相关，且超过未偶联的普通脂质体。ha脂质体通过脂质筏介导的内吞作用被吸收到细胞中，这是能量和胆固醇依赖的。一旦进入细胞，ha脂质体主要定位于核内体和溶酶体。结果表明，HA脂质体的细胞靶向效率在很大程度上取决于HA分子量、接枝密度和细胞表面受体CD44密度。结果支持ha脂质体在靶向药物递送中的作用。
Hyaluronan (HA) is a biocompatible and biodegradable linear polysaccharide which is of interest for tumor targeting through cell surface CD44 receptors. HA binds with high affinity to CD44 receptors, which are overexpressed in many tumors and involved in cancer metastasis. In the present study, we investigated the impact of HA molecular weight (MW), grafting density, and CD44 receptor density on endocytosis of HA-grafted liposomes (HA-liposomes) by cancer cells. Additionally, the intracellular localization of the HA-liposomes was determined. HAs of different MWs (5-8, 10-12, 175-350, and 1600 kDa) were conjugated to liposomes with varying degrees of grafting density. HA surface density was quantified using the hexadecyltrimethylammonium bromide turbidimetric method. Cellular uptake and subcellular localization of HA-liposomes were evaluated by flow cytometry and fluorescence microscopy. Mean particle sizes of HA-liposomes ranged from 120 to 180 nm and increased with the bigger size of HA. HA-liposome uptake correlated with HA MW (5-8 < 10-12 < 175-350 kDa), grafting density, and CD44 receptor density and exceeded that obtained with unconjugated plain liposomes. HA-liposomes were taken up into cells via lipid raft-mediated endocytosis, which is both energy- and cholesterol-dependent. Once within cells, HA-liposomes localized primarily to endosomes and lysosomes. The results demonstrate that cellular targeting efficiency of HA-liposomes depends strongly upon HA MW, grafting density, and cell surface receptor CD44 density. The results support a role of HA-liposomes for targeted drug delivery.
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影响因子：
10.8
作者：
Chono, Sumio;Li, Shyh-Dar;Conwell, Christine C.;Huang, Leaf
通讯作者：
Huang, Leaf
影响因子：
2.9
作者：
Arnold, Frank;Jia, Chiyu;West, David C.
通讯作者：
West, David C.
DOI：
10.1016/0005-2736(91)90246-5
发表时间：
1991-07-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
ALLEN, TM;HANSEN, C;YAUYOUNG, A
通讯作者：
YAUYOUNG, A
影响因子：
10.8
作者：
Huth, US;Schubert, R;Peschka-Süss, R
通讯作者：
Peschka-Süss, R
影响因子：
2.9
作者：
La Gatta, Annalisa;De Rosa, Mario;Schiraldi, Chiara
通讯作者：
Schiraldi, Chiara