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

Published

Journal 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.

Full Text

Duke Authors

Cited Authors

  • Evans, BC; Fletcher, RB; Kilchrist, KV; Dailing, EA; Mukalel, AJ; Colazo, JM; Oliver, M; Cheung-Flynn, J; Brophy, CM; Tierney, JW; Isenberg, JS; Hankenson, KD; Ghimire, K; Lander, C; Gersbach, CA; Duvall, CL

Published Date

  • November 2019

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 5012 -

PubMed ID

  • 31676764

Pubmed Central ID

  • 31676764

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-12906-y

Language

  • eng