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

Pharmaceuticals

Alfredo Erazo-Oliveras¹  Nandhini Muthukrishnan¹  Ryan Baker¹  Ting-Yi Wang² 

[1] Department of Biochemistry and Biophysics, Texas A&M University, Room 430, 300 Olsen Blvd., College Station, TX 77843-2128, USA;

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

DOI  :  10.3390/ph5111177

来源: mdpi

【 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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.