EGFR Targeting and Shielding of pDNA Lipopolyplexes via Bivalent Attachment of a Sequence-Defined PEG Agent

Macromol Biosci. 2018 Jan;18(1). doi: 10.1002/mabi.201700203. Epub 2017 Sep 6.


For successful nonviral gene delivery, cationic polymers are promising DNA carrier, which need to comprise several functionalities. The current work focuses on the postincorporation of epidermal growth factor receptor (EGFR) targeted PEGylation agents onto lipopolyplexes for pDNA delivery. T-shaped lipo-oligomers are previously found to be effective sequence-defined carriers for pDNA and siRNA. Here, the bis-oleoyl-oligoaminoethanamide 454 containing tyrosine trimer-cysteine ends is applied for complex formation with pDNA coding for luciferase or sodium iodide symporter (NIS). In a second step, the lipopolyplexes are modified via disulfide formation with sequence-defined monovalent or bivalent PEGylation agents containing one or two 3-nitro-2-pyridinesulfenyl (NPys)-activated cysteines, respectively. For targeting, the polyethylene glycol (PEG) agents comprise the EGFR targeting peptide GE11. In comparison of all transfection complexes, 454 lipopolyplexes modified with the bidentate PEG-GE11 agent show the best, EGFR-dependent uptake as well as luciferase and NIS gene expression into receptor-positive tumor cells.

Keywords: PEGylation; epidermal growth factor; gene delivery; nanoparticle; polyplex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Gene Expression Regulation / drug effects
  • Gene Transfer Techniques*
  • Genetic Therapy*
  • Humans
  • Iodine Radioisotopes / chemistry
  • Plasmids / genetics
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry
  • Polymers / therapeutic use
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / therapeutic use
  • Symporters / chemistry
  • Symporters / therapeutic use
  • Transfection


  • Iodine Radioisotopes
  • Polymers
  • RNA, Small Interfering
  • Symporters
  • Polyethylene Glycols
  • sodium-iodide symporter
  • EGFR protein, human
  • ErbB Receptors