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An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles

Peptides and biologics provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. Most peptides and biologics are fused with cationic uptake moieties or formulated into nanoparticles to facilitate delivery, but these systems typically lack potency d...

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Autores principales: Evans, Brian C., Fletcher, R. Brock, Kilchrist, Kameron V., Dailing, Eric A., Mukalel, Alvin J., Colazo, Juan M., Oliver, Matthew, Cheung-Flynn, Joyce, Brophy, Colleen M., Tierney, John W., Isenberg, Jeffrey S., Hankenson, Kurt D., Ghimire, Kedar, Lander, Cynthia, Gersbach, Charles A., Duvall, Craig L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825215/
https://www.ncbi.nlm.nih.gov/pubmed/31676764
http://dx.doi.org/10.1038/s41467-019-12906-y
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author Evans, Brian C.
Fletcher, R. Brock
Kilchrist, Kameron V.
Dailing, Eric A.
Mukalel, Alvin J.
Colazo, Juan M.
Oliver, Matthew
Cheung-Flynn, Joyce
Brophy, Colleen M.
Tierney, John W.
Isenberg, Jeffrey S.
Hankenson, Kurt D.
Ghimire, Kedar
Lander, Cynthia
Gersbach, Charles A.
Duvall, Craig L.
author_facet Evans, Brian C.
Fletcher, R. Brock
Kilchrist, Kameron V.
Dailing, Eric A.
Mukalel, Alvin J.
Colazo, Juan M.
Oliver, Matthew
Cheung-Flynn, Joyce
Brophy, Colleen M.
Tierney, John W.
Isenberg, Jeffrey S.
Hankenson, Kurt D.
Ghimire, Kedar
Lander, Cynthia
Gersbach, Charles A.
Duvall, Craig L.
author_sort Evans, Brian C.
collection PubMed
description Peptides and biologics provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. Most peptides and biologics are fused with cationic uptake moieties or formulated into nanoparticles to facilitate delivery, but these systems typically lack potency due to low uptake and/or entrapment and degradation in endolysosomal compartments. Because most delivery reagents comprise cationic lipids or polymers, there is a lack of reagents specifically optimized to deliver cationic cargo. Herein, we demonstrate the utility of the cytocompatible polymer poly(propylacrylic acid) (PPAA) to potentiate intracellular delivery of cationic biomacromolecules and nano-formulations. This approach demonstrates superior efficacy over all marketed peptide delivery reagents and enhances delivery of nucleic acids and gene editing ribonucleoproteins (RNPs) formulated with both commercially-available and our own custom-synthesized cationic polymer delivery reagents. These results demonstrate the broad potential of PPAA to serve as a platform reagent for the intracellular delivery of cationic cargo.
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spelling pubmed-68252152019-11-04 An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles Evans, Brian C. Fletcher, R. Brock Kilchrist, Kameron V. Dailing, Eric A. Mukalel, Alvin J. Colazo, Juan M. Oliver, Matthew Cheung-Flynn, Joyce Brophy, Colleen M. Tierney, John W. Isenberg, Jeffrey S. Hankenson, Kurt D. Ghimire, Kedar Lander, Cynthia Gersbach, Charles A. Duvall, Craig L. Nat Commun Article Peptides and biologics provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. Most peptides and biologics are fused with cationic uptake moieties or formulated into nanoparticles to facilitate delivery, but these systems typically lack potency due to low uptake and/or entrapment and degradation in endolysosomal compartments. Because most delivery reagents comprise cationic lipids or polymers, there is a lack of reagents specifically optimized to deliver cationic cargo. Herein, we demonstrate the utility of the cytocompatible polymer poly(propylacrylic acid) (PPAA) to potentiate intracellular delivery of cationic biomacromolecules and nano-formulations. This approach demonstrates superior efficacy over all marketed peptide delivery reagents and enhances delivery of nucleic acids and gene editing ribonucleoproteins (RNPs) formulated with both commercially-available and our own custom-synthesized cationic polymer delivery reagents. These results demonstrate the broad potential of PPAA to serve as a platform reagent for the intracellular delivery of cationic cargo. Nature Publishing Group UK 2019-11-01 /pmc/articles/PMC6825215/ /pubmed/31676764 http://dx.doi.org/10.1038/s41467-019-12906-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Evans, Brian C.
Fletcher, R. Brock
Kilchrist, Kameron V.
Dailing, Eric A.
Mukalel, Alvin J.
Colazo, Juan M.
Oliver, Matthew
Cheung-Flynn, Joyce
Brophy, Colleen M.
Tierney, John W.
Isenberg, Jeffrey S.
Hankenson, Kurt D.
Ghimire, Kedar
Lander, Cynthia
Gersbach, Charles A.
Duvall, Craig L.
An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles
title An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles
title_full An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles
title_fullStr An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles
title_full_unstemmed An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles
title_short An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles
title_sort anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825215/
https://www.ncbi.nlm.nih.gov/pubmed/31676764
http://dx.doi.org/10.1038/s41467-019-12906-y
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