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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

Nature communications, 2019-11, Vol.10 (1), p.5012-19, Article 5012 [Periódico revisado por pares]

England: Nature Publishing Group

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An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles
Autor: 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
Assuntos: Acrylates - chemistry ; Animals ; Anions - chemistry ; Cargo ; Cationic peptides ; Cationic polymerization ; Cations - chemistry ; Cell Line ; Cells, Cultured ; Drug Delivery Systems - methods ; Endosomes - chemistry ; Endosomes - metabolism ; Entrapment ; Genetic modification ; HEK293 Cells ; Humans ; Intracellular ; Intracellular Space - metabolism ; Lipids ; Macromolecular Substances - administration & dosage ; Macromolecular Substances - chemistry ; MCF-7 Cells ; Mice ; Nanoparticles ; Nanoparticles - administration & dosage ; Nanoparticles - chemistry ; NIH 3T3 Cells ; Nucleic acids ; Peptides ; Peptides - administration & dosage ; Peptides - chemistry ; Polymers ; Polymers - chemistry ; Rats ; RAW 264.7 Cells ; Reagents ; Reproducibility of Results ; Ribonucleoproteins
É parte de: Nature communications, 2019-11, Vol.10 (1), p.5012-19, Article 5012
Descrição: 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.
Editor: England: Nature Publishing Group
Idioma: Inglês

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

England: Nature Publishing Group

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