Peptide T7-modified polypeptide with disulfide bonds for targeted delivery of plasmid DNA for gene therapy of prostate cancer

Int J Nanomedicine. 2018 Oct 30:13:6913-6927. doi: 10.2147/IJN.S180957. eCollection 2018.

Abstract

Background: Vectors are essential for successful gene delivery. In the present study, a tumor-targeting cationic gene vector, known as the disulfide cross-linked arginine-aspartic acid peptide modified by HAIYPRH (T7) peptide (CRD-PEG-T7), was designed for targeted delivery of plasmid DNA (pDNA) for gene therapy of prostate cancer (PCa).

Methods: The structure of CRD-PEG-T7 was determined and the cellular uptake efficacy, gene transfection efficacy, cytotoxicity, and the targeting effect of the CRD-PEG-T7-plasmid DNA complex were examined.

Results: The results demonstrated that the CRD-PEG-T7-plasmid DNA complex was nanosized and had a positively charged surface, good cellular uptake efficacy, minimal cytotoxicity, and a dual-targeting effect as compared with the CRD-PEG-plasmid DNA complex. The peptide T7-modifed new delivery system was able to target the highly expressed transferrin receptor (TfR) on tumor cells with an efficiency four-fold higher than that of the non-modified system.

Conclusion: The results above indicatd that the CRD-PEG-T7-plasmid DNA complex may prove to be a promising gene delivery system targeting bone-metastatic tumor.

Keywords: DNA delivery; arginine peptide; aspartic acid peptide; bone metastasis prostate cancer; tumor targeting.

MeSH terms

  • Animals
  • Benzoxazoles / chemistry
  • Cell Death
  • Cell Line, Tumor
  • Cell Movement
  • Collagen Type IV / chemical synthesis
  • Collagen Type IV / chemistry*
  • DNA / administration & dosage*
  • DNA / genetics*
  • Disulfides / chemistry*
  • Endocytosis
  • Gene Transfer Techniques*
  • Genetic Therapy*
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Particle Size
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry*
  • Plasmids / administration & dosage*
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Proton Magnetic Resonance Spectroscopy
  • Quinolinium Compounds / chemistry
  • Static Electricity
  • Tissue Distribution
  • Transfection
  • Transferrin / chemistry

Substances

  • Benzoxazoles
  • Collagen Type IV
  • Disulfides
  • Peptide Fragments
  • Quinolinium Compounds
  • Transferrin
  • tumstatin (74-98)
  • 1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium
  • Polyethylene Glycols
  • DNA