Comparison of Cellular Uptake Using 22 CPPs in 4 Different Cell Lines
Comparison of Cellular Uptake Using 22 CPPs in 4 Different Cell Lines
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DOI：
10.1021/bc800194e
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发表时间：
2008-12-01
影响因子：
4.7
通讯作者：
Boisguerin, Prisca
中科院分区：
文献类型：
--
作者：
Mueller, Judith;Kretzschmar, Ines;Boisguerin, Prisca
细胞穿透性多肽(CPPs)是一类能够穿透细胞膜并将不同的物质转运到细胞内的短肽。虽然最近许多研究文章都是这个主题，但据我们所知，迄今还没有对CPP进行单一的系统研究，这意味着只能从不同的来源逐段收集信息。因此，我们决定开始对细胞系中CPP的特异性进行分析筛选。我们使用了22种不同的CPP，这些都是以前发表过的，并在4个选定的细胞系(MDCK、HEK293、HeLa和Cos-7)中展示了第一个分析屏幕。此外，我们还考察了不同条件的影响，如酶抑制剂、孵育条件、内吞作用抑制剂、温度和细胞毒性。我们清楚地证明，即使在胰酶消化后，22个CPP也可以根据它们的内化特性分为3类。此外，我们还表明，应该增加细胞摄取或溶解包裹CPPS的内体/溶酶体的其他药物只有很低的效果。我们在标准化条件下的密集筛选为比较细胞对CPPs的摄取提供了机会，这是将CPPs用作医疗领域多肽载体的重要一步。
Cell-penetrating peptides (CPPs) are short peptides able to penetrate cell membranes and translocate different cargoes into cells. Although recently the topic of many research articles, to our best knowledge no single systematic study of CPPs has been carried out as yet, meaning information can only by gathered piece by piece from different sources. We therefore decided to start analytical screening of CPP specificity in cell lines. We used 22 different CPPs, which have all been published before, and present the first analytical screen in 4 selected cell lines (MDCK, HEK293, HeLa, and Cos-7). Furthermore, we examined the influence of different conditions, such as protease inhibitors, incubation conditions, endocytosis inhibitors, temperature, and cytotoxicity. We clearly demonstrate that the 22 CPPs can be classified into 3 groups based on their internalization properties, even after trypsinization. Moreover, we show that additional agents, which should increase cellular uptake or dissolve endosomal/lysosomal entrapped CPPs, only have low effects. Our intensive screening under standardized conditions provides the opportunity to compare cellular uptake of CPPs, an important step for the use of CPPs as peptidic vectors in the medical field.