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Rational design of a biomimetic cell penetrating peptide library.

Authors
  • Karagiannis, Emmanouil D1
  • Urbanska, Aleksandra M
  • Sahay, Gaurav
  • Pelet, Jeisa M
  • Jhunjhunwala, Siddharth
  • Langer, Robert
  • Anderson, Daniel G
  • 1 David H. Koch Institute for Integrative Cancer Research, ‡Department of Chemical Engineering, and §Division of Health Science and Technology, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02142, United States. , (United States)
Type
Published Article
Journal
ACS Nano
Publisher
American Chemical Society
Publication Date
Oct 22, 2013
Volume
7
Issue
10
Pages
8616–8626
Identifiers
DOI: 10.1021/nn4027382
PMID: 24047542
Source
Medline
License
Unknown

Abstract

Cell penetrating peptides have demonstrated potential to facilitate the cellular delivery of therapeutic molecules. Here we develop a set of 50 cell penetrating peptide based formulations with potential to deliver small interfering RNAs intercellularly. The transfection efficacy of siRNA containing lipid-like nanoparticles decorated with different peptides was evaluated both in vitro and in vivo and correlated with the peptide physical and chemical properties. In vitro, these particles were internalized primarily through macropinocytosis. When the peptides were presented to bone marrow-derived dendritic cells, they induce low immunoactivation relative to control cell penetrating peptides including the antennapedia homeodomain and TAT, as quantified by the expression of activation specific surface proteins like CD80, CD86, and major histocompatibility complex class II. In vivo, peptide decorated nanoparticles primarily accumulated in the lungs and the liver. Three human peptides derived from surfactant protein B (a lung surfactant protein), orexin (a neuropeptide hormone, and lactoferricin (a globular glycoprotein) that exist in many physiological fluids facilitated the in vivo delivery of siRNA and induce significant knock down (90%) of a hepatocyte expressed protein, coagulation Factor VII.

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