Improving the Endosomal Escape of Cell-Penetrating Peptides and Their Cargos: Strategies and Challenges

被引：334

作者：

Erazo-Oliveras, Alfredo ^{[1
]}

Muthukrishnan, Nandhini ^{[1
]}

Baker, Ryan ^{[1
]}

Wang, Ting-Yi ^{[1
]}

Pellois, Jean-Philippe ^{[1
]}

机构：

[1] Texas A&M Univ, Dept Biochem & Biophys, Room 430,300 Olsen Blvd, College Stn, TX 77843 USA

来源：

PHARMACEUTICALS | 2012年 / 5卷 / 11期

关键词：

endosomal escape; cell-penetrating peptide; photochemical internalization; multivalent peptides; pH-dependent membrane-active peptides;

D O I：

10.3390/ph5111177

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

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.

引用

页码：1177 / 1209

页数：33

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