Biodistribution and Tumor Localization of PEG-Modified Dendritic Poly(L-Lysine) Oligonucleotide Complexes

J Biomater Sci Polym Ed. 2012;23(18):2369-80. doi: 10.1163/156856211X617722. Epub 2012 May 11.

Abstract

A poly(ethylene glycol) (PEG)-modified dendritic poly(L-lysine) (PEG-WeKG6) containing tryptophan residues in its core was synthesized as an oligonucleotide carrier to tumors after systemic injection. PEG- WeKG6 formed a stable complex with double-stranded deoxyoligonucleotide (ODN). The size and the zeta-potential of the complex were smaller than those of a dendritic poly(L-lysine) without PEG (WeKG6). To study the biodistribution of the complexes in tumor-bearing mice after intravenous injection, the den- drimers and the oligonucleotide were labeled with gadolinium and Cy5, respectively. Our results show that PEG modification of the dendrimer improved the stability of ODN in blood circulation. Effective accumulation of the PEG-WeKG6/ODN complex in the tumor tissue was found 24 h after the injection. These results indicate that PEG-WeKG6 is suitable for forming a complex with any genetic or therapeutic material for efficient delivery to tumors.

Keywords: Dendrimer; biodistribution; oligonucleotide; poly(ethylene glycol); tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Dendrimers / chemistry*
  • Drug Carriers / chemistry*
  • Male
  • Mice
  • Oligodeoxyribonucleotides / chemistry*
  • Oligodeoxyribonucleotides / genetics
  • Oligodeoxyribonucleotides / pharmacokinetics*
  • Polyethylene Glycols / chemistry*
  • Polylysine / chemistry*
  • Rectal Neoplasms / metabolism*
  • Rectal Neoplasms / pathology
  • Tissue Distribution

Substances

  • Dendrimers
  • Drug Carriers
  • Oligodeoxyribonucleotides
  • Polylysine
  • Polyethylene Glycols