Biomimetic glycoliposomes as nanocarriers for targeting P-selectin on activated platelets.
Biomimetic glycoliposomes as nanocarriers for targeting P-selectin on activated platelets.
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DOI：
10.1021/bc700212b
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发表时间：
2007-08
影响因子：
4.7
通讯作者：
Junmin Zhu;J. Xue;Zhongwu Guo;Linda Zhang;R. Marchant
中科院分区：
文献类型：
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作者：
Junmin Zhu;J. Xue;Zhongwu Guo;Linda Zhang;R. Marchant
细胞糖萼是一个有吸引力的模型，表面修饰的脂质体的目标是组织靶向和延长循环时间。在这里，我们报道了糖萼模拟脂质体，通过将糖脂3'-磺基-Lewis a（SuLe（a））-PEG-DSPE与SuLe（a）的头基和连接到两个疏水性尾部的聚乙二醇（PEG）的间隔基结合来制备。该PEG间隔结构用于模拟活化白细胞上的P-选择素糖蛋白配体1（PSGL-1）的延伸结构，以促进脂质体与活化血小板上表达的P-选择素受体的特异性结合。结果表明，SuLe（a）-PEG-DSPE可与1，2-二硬脂酰甘油磷酸胆碱（DSPC）和胆固醇形成稳定的窄分布脂质体，囊泡大小为113.3nm。所得的SuLe（a）-PEG-脂质体可以促进它们与P-选择素受体的结合，比没有PEG间隔物的SuLe（a）-脂质体高22倍。荧光显微镜观察表明，SuLe（a）-PEG-脂质体在体外能有效地与活化血小板结合。这表明，仿生SuLe（a）-PEG-脂质体可用作靶向活化血小板的纳米载体，用于将药物递送到心血管疾病的损伤部位。
The cell glycocalyx is an attractive model for surface modification of liposomes with the objectives of tissue targeting and prolonged circulation time. Here, we reported on glycocalyx-mimicking liposomes, prepared by incorporating a glycolipid of 3'-sulfo-Lewis a (SuLe(a))-PEG-DSPE with a headgroup of SuLe(a) and a spacer of poly(ethylene glycol) (PEG) linked to two hydrophobic tails. This PEG spaced structure is used to mimic the extended structure of P-selectin glycoprotein ligand 1 (PSGL-1) on activated leukocytes, in order to facilitate the specific binding of liposomes to the receptor of P-selectin expressed on activated platelets. Our results indicate that SuLe(a)-PEG-DSPE can form stable, narrowly distributed liposomes with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol, with a vesicle size of 113.3 nm. The resultant SuLe(a)-PEG-liposomes can facilitate their binding to the receptor of P-selectin 22 times higher than SuLe(a)-liposomes without a PEG spacer. Further studies by fluorescence microscopy show that SuLe(a)-PEG-liposomes can bind to activated platelets in vitro effectively. It suggests that biomimetic SuLe(a)-PEG-liposomes may be used as nanocarriers to target activated platelets for drug delivery to the injury sites of cardiovascular diseases.