Improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges. Academic Article

abstract

• 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.

authors

• Pellois, Jean-Philippe

published proceedings

• Pharmaceuticals (Basel)

altmetric score

• 15

author list (cited authors)

• Erazo-Oliveras, A., Muthukrishnan, N., Baker, R., Wang, T., & Pellois, J.

citation count

• 286

complete list of authors

• Erazo-Oliveras, Alfredo||Muthukrishnan, Nandhini||Baker, Ryan||Wang, Ting-Yi||Pellois, Jean-Philippe

publication date

• January 2012

publisher

• MDPI  Publisher

published in

• Pharmaceuticals  Journal

keywords

• Cell-penetrating Peptide
• Endosomal Escape
• Multivalent Peptides
• Ph-dependent Membrane-active Peptides
• Photochemical Internalization

Digital Object Identifier (DOI)

• 10.3390/ph5111177

start page

• 1177

end page

• 1209

volume

• 5

issue

• 11

URL

• http%3A%2F%2Fdx.doi.org%2F10.3390%2Fph5111177