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Selecting improved peptidyl motifs for cytosolic delivery of disparate protein and nanoparticle materials

Academic Article
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Overview

authors

  • Boeneman, K.
  • Delehanty, J. B.
  • Blanco-Canosa, J. B.
  • Susumu, K.
  • Stewart, M. H.
  • Oh, E.
  • Huston, A. L.
  • Dawson, G.
  • Ingale, S.
  • Walters, R.
  • Domowicz, M.
  • Deschamps, J. R.
  • Algar, W. R.
  • DiMaggio, S.
  • Manono, J.
  • Spillmann, C. M.
  • Thompson, D.
  • Jennings, T. L.
  • Dawson, Philip
  • Medintz, I. L.

publication date

  • May 2013

journal

  • ACS Nano  Journal

abstract

  • Cell penetrating peptides facilitate efficient intracellular uptake of diverse materials ranging from small contrast agents to larger proteins and nanoparticles. However, a significant impediment remains in the subsequent compartmentalization/endosomal sequestration of most of these cargoes. Previous functional screening suggested that a modular peptide originally designed to deliver palmitoyl-protein thioesterase inhibitors to neurons could mediate endosomal escape in cultured cells. Here, we detail properties relevant to this peptide's ability to mediate cytosolic delivery of quantum dots (QDs) to a wide range of cell-types, brain tissue culture and a developing chick embryo in a remarkably nontoxic manner. The peptide further facilitated efficient endosomal escape of large proteins, dendrimers and other nanoparticle materials. We undertook an iterative structure-activity relationship analysis of the peptide by discretely modifying key components including length, charge, fatty acid content and their order using a comparative, semiquantitative assay. This approach allowed us to define the key motifs required for endosomal escape, to select more efficient escape sequences, along with unexpectedly identifying a sequence modified by one methylene group that specifically targeted QDs to cellular membranes. We interpret our results within a model of peptide function and highlight implications for in vivo labeling and nanoparticle-mediated drug delivery by using different peptides to co-deliver cargoes to cells and engage in multifunctional labeling.

subject areas

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell-Penetrating Peptides
  • Chick Embryo
  • Cytosol
  • Drug Carriers
  • Endosomes
  • Humans
  • Maltose-Binding Proteins
  • Molecular Sequence Data
  • Quantum Dots
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Research

keywords

  • cargo
  • cell penetrating peptide
  • cellular labeling
  • cytosol
  • dendrimer
  • endosomal escape
  • fusogenic
  • membrane
  • nanoparticle
  • peptide
  • protein
  • quantum dot
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Identity

PubMed Central ID

  • PMC3880025

International Standard Serial Number (ISSN)

  • 1936-0851

Digital Object Identifier (DOI)

  • 10.1021/nn400702r

PubMed ID

  • 23710591
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Additional Document Info

start page

  • 3778

end page

  • 3796

volume

  • 7

issue

  • 5

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