Effects of the gene carrier polyethyleneimines on structure and function of blood components.
Effects of the gene carrier polyethyleneimines on structure and function of blood components.
复制标题
DOI：
10.1016/j.biomaterials.2012.09.060
复制
发表时间：
2013
期刊：
影响因子：
14
通讯作者：
Dagen Zhong;Y. Jiao;Yi Zhang;Wei Zhang;Nan Li;Qinhua Zuo;Qian Wang;Wei Xue;Zong-hua Liu-Zong-hua-Li
中科院分区：
文献类型：
--
作者：
Dagen Zhong;Y. Jiao;Yi Zhang;Wei Zhang;Nan Li;Qinhua Zuo;Qian Wang;Wei Xue;Zong-hua Liu-Zong-hua-Li
聚乙烯亚胺（PEI）作为一种合成多阳离子，是目前最有效的非病毒基因载体之一。在体内应用时，PEI会进入体循环，与各种血液成分相互作用，进而影响其个体生物功能。尽管PEI与多种血液成分在细胞、膜和分子水平上的相互作用对PEI的体内安全性至关重要，但目前还缺乏对PEI与多种血液成分相互作用的全面、系统的研究。为了了解结构-活性关系，我们研究了不同分子量（MW）和形状（支状或线性）的PEI对血液关键成分和功能的影响，特别是对红细胞聚集和形态改变、血小板活化、白蛋白构象改变（作为血浆蛋白的代表）和血液凝固过程的影响。此外，通过蛋白质组学分析，从血浆中筛选并鉴定出更多与PEI相关的蛋白质。研究发现，PEIs对红细胞膜结构、白蛋白构象和凝血过程有严重影响，但在低浓度下不显著激活血小板。此外，41个血浆蛋白被鉴定出与PEI有一定的相互作用。这表明，除了白蛋白外，PEI还与多种血浆蛋白相互作用，并可能对其结构和生物功能产生未知的影响。该结果为PEI和其他聚合体在体内应用的分子设计和血液安全性提供了很好的见解。
As a synthetic polycation, polyethylenimine (PEI) is currently one of the most effective non-viral gene carriers. For in vivo applications, PEI will enter systemic circulation and interact with various blood components and then affect their individual bio-functions. Up to now, overall and systematic investigation on the interaction of PEI with multiple blood components at cellular, membrane, and molecular levels is lacking, even though it is critically important for the in vivo safety of PEI. To learn a structure–activity relationship, we investigated the effects of PEI with different molecular weight (MW) and shape (branched or linear) on key blood components and function, specifically, on RBC aggregation and morphological change, platelet activation, conformation change of albumin (as a representative of plasma proteins), and blood coagulation process. Additionally, more proteins from plasma were screened and identified to have associations with PEI by a proteomic analysis. It was found that, the PEIs have severe impact on RBC membrane structure, albumin conformation, and blood coagulation process, but do not significantly activate platelets at low concentrations. Furthermore, 41 plasma proteins were identified to have some interaction with PEI. This indicates that, besides albumin, PEI does interact with a variety of blood plasma proteins, and could have unexplored effects on their structures and bio-functions. The results provide good insight into the molecular design and blood safety of PEI and other polycations for in vivo applications.