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June 14, 2017PolymersOpen Access

Polyamidoamine (PAMAM) Dendrimers Modified with Cathepsin-B Cleavable Oligopeptides for Enhanced Gene Delivery

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Authors

SLSeulgi LeeSSSang Jun SonSSSu Jeong Song

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Overview

In vitro study demonstrates enhanced gene transfection and reduced cytotoxicity in HeLa cells using peptide-modified PAMAM dendrimers, indicating potential for targeted cancer gene therapy.

Key Points

  • To synthesize and evaluate a cathepsin B-responsive PAMAM G4 dendrimer conjugated with histidine and arginine for enhanced, low-toxicity gene delivery.
  • Conjugated generation 4 PAMAM dendrimers with a cathepsin B-cleavable peptide sequence (GFLG), histidine for endosomal escape, and arginine for cellular uptake (G4-GLFG-H-R), verified via 1H-NMR spectroscopy.
  • Formed polyplexes between G4-GLFG-H-R and plasmid DNA (pDNA), assessing enzyme-triggered release and endosomal escape using gel electrophoresis.
  • Evaluated transfection efficiency and cytotoxicity in HeLa cell cultures compared to unmodified G4 dendrimer controls.
  • Gel electrophoresis confirmed that exposure to cathepsin B triggered pDNA release from the G4-GLFG-H-R polyplex, facilitating endosomal escape.
  • Enzyme-sensitive G4-GLFG-H-R polyplexes produced higher transfection efficiency in HeLa cells than unmodified G4 controls.
  • G4-GLFG-H-R exhibited lower cytotoxicity in HeLa cells compared to the unmodified G4 dendrimer control.

Cite This Study

Lee et al. (2017) studied this question.

synapsesocial.com/papers/6aaf2ef6c3eca59fee25ce74https://doi.org/10.3390/polym9060224
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