Shear-regulated uptake of nanoparticles by endothelial cells and development of endothelial-targeting nanoparticles.
Shear-regulated uptake of nanoparticles by endothelial cells and development of endothelial-targeting nanoparticles.
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DOI：
10.1002/jbm.a.32592
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发表时间：
2010-06-01
影响因子：
4.9
通讯作者：
Nguyen, Kytai T.
中科院分区：
文献类型：
--
作者：
Lin, Arthur;Sabnis, Abhimanyu;Kona, Soujanya;Nattama, Sivaniaravindapriya;Patel, Hemang;Dong, Jing-Fei;Nguyen, Kytai T.
该研究项目的目的是开发在生理流动条件下具有改善的靶向、粘附和细胞摄取的纳米颗粒，以激活或发炎的内皮细胞（EC）。我们的假设是，通过血小板糖蛋白Ibα（GP Ibα）和活化内皮细胞上的P-选择素之间的相互作用模拟血小板与活化内皮细胞的结合，GP Ibα缀合的纳米颗粒可以在生理流动条件下在损伤或活化的内皮细胞中表现出更高的靶向性和更高的细胞摄取。为了检验这一假设，选择荧光羧化聚苯乙烯纳米颗粒作为研究的模型颗粒，因为它的窄尺寸分布作为“概念验证”。使用共聚焦显微镜，荧光测量，和蛋白质测定，细胞摄取特性的特征在于这些聚苯乙烯纳米颗粒。该研究还发现，将100 nm聚苯乙烯纳米颗粒与glycocalicin（GP Ibα的细胞外片段）结合，可显著增加颗粒在P-选择素包被表面上的粘附，并在生理流动条件下通过活化的内皮细胞对纳米颗粒的细胞摄取。结果表明，这些新型内皮靶向纳米颗粒可能是开发靶向和持续药物递送系统的第一步，该系统可以改善剪切调节的颗粒粘附和细胞摄取。
The purpose of this research project was to develop nanoparticles with improved targeting, adhesion, and cellular uptake to activated or inflamed endothelial cells (ECs) under physiological flow conditions. Our hypothesis is that by mimicking platelet binding to activated ECs through the interaction between platelet glycoprotein Ibα (GP Ibα) and P-selectin on activated endothelial cells, GP Ibα-conjugated nanoparticles could exhibit increased targeting and higher cellular uptake in injured or activated endothelial cells under physiological flow conditions. To test this hypothesis, fluorescent carboxylated polystyrene nanoparticles were selected for the study as a model particle due to its narrow size distribution as a “proof-of-concept”. Using confocol microscopy, fluorescent measurement, and protein assays, cellular uptake properties were characterized for these polystyrene nanoparticles. The study also found that conjugation of 100 nm polystyrene nanoparticles with glycocalicin (the extracellular segment of GP Ibα) significantly increased the particle adhesion on P-selectin-coated surfaces and cellular uptake of nanoparticles by activated endothelial cells under physiological flow conditions. The results demonstrate that these novel endothelial-targeting nanoparticles could be the first step towards developing a targeted and sustained drug delivery system that can improve shear-regulated particle adhesion and cellular uptake.
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影响因子：
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作者：
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通讯作者：
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