Improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges.
Improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges.
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DOI：
10.3390/ph5111177
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发表时间：
2012-11-01
期刊：
影响因子：
--
通讯作者：
Pellois JP
中科院分区：
文献类型：
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作者：
Erazo-Oliveras A;Muthukrishnan N;Baker R;Wang TY;Pellois JP
细胞穿透肽（CPP）可以将细胞不可渗透的治疗物质递送到细胞中。特别地，CPP-货物缀合物倾向于通过内吞作用在细胞内积累。然而，它们通常被困在内吞细胞器内，不能有效地到达细胞的胞质空间。在这篇综述中，CPP介导的内体逃逸的证据进行了讨论。此外，已被用来提高CPP-货物的内体逃逸的几种策略进行了描述。介绍了显示CPP多拷贝的分支系统的最新发展。还讨论了使用病毒或合成肽，其可以在通过低pH值的内体激活后破坏内体膜。最后，我们调查了如何与发色团标记的CPP可以与光结合使用，以刺激内体裂解。讨论了与这些细胞内递送方法相关的机制和挑战。
Cell penetrating peptides (CPPs) can deliver cell-impermeable therapeutic cargos into cells. In particular, CPP-cargo conjugates tend to accumulate inside cells by endocytosis. However, they often remain trapped inside endocytic organelles and fail to reach the cytosolic space of cells efficiently. In this review, the evidence for CPP-mediated endosomal escape is discussed. In addition, several strategies that have been utilized to enhance the endosomal escape of CPP-cargos are described. The recent development of branched systems that display multiple copies of a CPP is presented. The use of viral or synthetic peptides that can disrupt the endosomal membrane upon activation by the low pH of endosomes is also discussed. Finally, we survey how CPPs labeled with chromophores can be used in combination with light to stimulate endosomal lysis. The mechanisms and challenges associated with these intracellular delivery methodologies are discussed.