RPM peptide conjugated bioreducible polyethylenimine targeting invasive colon cancer

J Control Release. 2015 May 10:205:172-80. doi: 10.1016/j.jconrel.2015.01.020. Epub 2015 Jan 21.

Abstract

CPIEDRPMC (RPM) peptide is a peptide that specifically targets invasive colorectal cancer, which is one of the leading causes of cancer-related deaths worldwide. In this study, we exploited RPM peptide as a targeting ligand to produce a novel and efficient gene delivery system that could potentially be used to treat invasive colon cancer. In order to achieve enhanced specificity to colon cancer cells, the RPM peptide was conjugated to a bioreducible gene carrier consisting of a reducible moiety of disulfide-crosslinked low molecular weight polyethylenimine, IR820 dye, and polyethylene glycol. Here, we examined the physiochemical properties, cytotoxicity, in vitro transfection efficiency, and in vivo biodistribution of the RPM-conjugated polyplex. Our results showed that the RPM-conjugated gene carrier formed a compact polyplex with pDNA that had low toxicity. Furthermore, the RPM-conjugated polymer not only had higher cellular uptake in invasive colon cancer than the non-targeted polymer, but also showed enhanced transfection efficiency in invasive colon cancer cells in vitro and in vivo.

Keywords: Bioreducible polymer; Colorectal cancer; Gene delivery; RPM peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Coloring Agents / chemistry
  • Coloring Agents / metabolism
  • Genetic Therapy / methods*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Indocyanine Green / analogs & derivatives
  • Indocyanine Green / chemistry
  • Indocyanine Green / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Nucleic Acid Conformation
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Oligopeptides / pharmacokinetics
  • Oxidation-Reduction
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / metabolism*
  • Peptides, Cyclic / pharmacokinetics
  • Plasmids / chemistry
  • Plasmids / genetics
  • Plasmids / metabolism*
  • Polyethylene Glycols / chemistry
  • Polyethyleneimine / chemistry*
  • Tissue Distribution
  • Transfection / methods*
  • Xenograft Model Antitumor Assays

Substances

  • Coloring Agents
  • IR 820
  • Oligopeptides
  • Peptides, Cyclic
  • cysteinyl-prolyl-isoleucyl-glutamyl-aspartyl-arginyl-prolyl-methionyl-cysteine (1-9) disulfide
  • Polyethylene Glycols
  • Polyethyleneimine
  • Indocyanine Green