The transport pathways of polymer nanoparticles in MDCK epithelial cells
The transport pathways of polymer nanoparticles in MDCK epithelial cells
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聚合物纳米粒子在MDCK上皮细胞中的转运途径
DOI：
10.1016/j.biomaterials.2013.01.100
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发表时间：
2013-06-01
期刊：
影响因子：
14
通讯作者：
Zhang, Qiang
中科院分区：
文献类型：
--
作者：
He, Bing;Jia, Zengrong;Zhang, Qiang
上皮细胞膜作为典型的生物屏障，构成了包括纳米药物在内的治疗剂运输的主要障碍。尽管现在越来越多的口服纳米药物上市，但以往关于纳米药物与细胞相互作用的研究大多侧重于细胞摄取和细胞内运输，而很少关注上皮细胞。为了阐明纳米药物在上皮细胞中的转运途径，本文以一种聚合物纳米粒子（PNs）和MDCK上皮细胞为模型，仔细研究和比较了胞吞、胞吐和转胞吞过程之间的不同分子机制。结果证明了它们的相似性和差异性。这三个过程的相似之处包括脂筏的介导、一些蛋白激酶如蛋白酪氨酸激酶（PTK）、蛋白激酶C（PKC）和磷脂酰肌醇3-激酶（P13K）的参与，以及多种途径的存在。然而，这些过程之间的差异非常显着，包括不同的途径，特别是脂筏和蛋白激酶对不同过程的不同影响。内吞作用涉及脂筏和网格蛋白机制，但不涉及巨胞饮作用，通过膜内陷但不形成孔道，胞吐作用包括ER/Golgi和Golgi/PM途径，转胞吞作用包括AEE/CE/BSE和Golgi/BSE途径。脂筏对内吞作用呈正作用，而对胞吐作用和转胞吞作用则呈负作用。 PTK和PKC对内吞作用具有正向影响，而PTK、PKC和P13K对AEE/CE/BSE以及PTK和P13K对高尔基体/BSE转胞吞途径具有负向影响。此外，PNs向内和向外运输之间的差异阐明了一个有趣的事实，即内吞作用相当容易，而包括胞吐作用和转胞吞作用在内的向外运输则相当困难。最后，通过与以往报道的比较表明，PNs与蛋白质等大分子之间的分子机制也有所不同。 (C) 2013 Elsevier Ltd. 保留所有权利。
Epithelial cell membranes as the typical biological barrier constitute the prime obstacle for the transport of therapeutic agents including nanomedicines. The previous studies on the interaction between nanomedicines and cells are mostly emphasized on cellular uptake and intracellular trafficking, but seldom on epithelial cells, although more and more oral nanomedicines are available now. In an attempt to clarify the transport pathways of nanomedicines in epithelial cells, the different molecular mechanisms among endocytosis, exocytosis and transcytosis processes were carefully studied and compared here using a kind of polymer nanopartides (PNs) and MDCK epithelial cells as models. As the result, their similarity and difference were demonstrated. The similarities among all the three processes included the mediation of lipid rafts, the involvement of some protein kinases such as protein tyrosine kinase (PTK), protein kinase C (PKC) and phosphatidylinositol 3-kinase (P13K), and the existence of multiple pathways. However, the difference among these processes was very significant, including different pathways, and especially the disparate effects of lipid rafts and protein kinases for different processes. The endocytosis involved both lipid raft and clathrin mechanisms but no macropinocytosis, via the invagination of membrane but no pore formation, the exocytosis contained ER/Golgi and Golgi/PM pathways, and transcytosis included AEE/CE/BSE and Golgi/BSE pathways. The roles of lipid rafts on endocytosis were positive but that on exocytosis and transcytosis was negative. The impacts of PTK and PKC on endocytosis were positive, while the influences of PTK, PKC and P13K on AEE/CE/BSE, as well as PTK and P13K on Golgi/BSE transcytosis pathways were negative. Moreover, the discrepancy between inward and outward transport of PNs elucidated an interesting fact that the endocytosis was rather easy and outward transport including exocytosis and transcytosis was rather difficult. Finally, it was indicated by comparison with previous reports that the molecular mechanisms between PNs and macromolecules such as proteins were also dissimilar. (C) 2013 Elsevier Ltd. All rights reserved.