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

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....

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Detalles Bibliográficos
Autores principales: Erazo-Oliveras, Alfredo, Muthukrishnan, Nandhini, Baker, Ryan, Wang, Ting-Yi, Pellois, Jean-Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816665/
https://www.ncbi.nlm.nih.gov/pubmed/24223492
http://dx.doi.org/10.3390/ph5111177
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author Erazo-Oliveras, Alfredo
Muthukrishnan, Nandhini
Baker, Ryan
Wang, Ting-Yi
Pellois, Jean-Philippe
author_facet Erazo-Oliveras, Alfredo
Muthukrishnan, Nandhini
Baker, Ryan
Wang, Ting-Yi
Pellois, Jean-Philippe
author_sort Erazo-Oliveras, Alfredo
collection PubMed
description 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.
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spelling pubmed-38166652013-11-06 Improving the Endosomal Escape of Cell-Penetrating Peptides and Their Cargos: Strategies and Challenges Erazo-Oliveras, Alfredo Muthukrishnan, Nandhini Baker, Ryan Wang, Ting-Yi Pellois, Jean-Philippe Pharmaceuticals (Basel) Review 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. MDPI 2012-11-01 /pmc/articles/PMC3816665/ /pubmed/24223492 http://dx.doi.org/10.3390/ph5111177 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Erazo-Oliveras, Alfredo
Muthukrishnan, Nandhini
Baker, Ryan
Wang, Ting-Yi
Pellois, Jean-Philippe
Improving the Endosomal Escape of Cell-Penetrating Peptides and Their Cargos: Strategies and Challenges
title Improving the Endosomal Escape of Cell-Penetrating Peptides and Their Cargos: Strategies and Challenges
title_full Improving the Endosomal Escape of Cell-Penetrating Peptides and Their Cargos: Strategies and Challenges
title_fullStr Improving the Endosomal Escape of Cell-Penetrating Peptides and Their Cargos: Strategies and Challenges
title_full_unstemmed Improving the Endosomal Escape of Cell-Penetrating Peptides and Their Cargos: Strategies and Challenges
title_short Improving the Endosomal Escape of Cell-Penetrating Peptides and Their Cargos: Strategies and Challenges
title_sort improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816665/
https://www.ncbi.nlm.nih.gov/pubmed/24223492
http://dx.doi.org/10.3390/ph5111177
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