Nanoparticulate delivery of suicide DNA to murine prostate and prostate tumors

Prostate. 2007 Jun 1;67(8):855-62. doi: 10.1002/pros.20576.

Abstract

Background: Currently available treatments for benign prostatic hyperplasia (BPH) and localized prostate cancer are generally effective but are often attended by serious side effects that impact on the quality of life. In particular, most current therapies are non-specific, with surgery, radiation, and chemical ablation having the potential to cause damage to surrounding tissue. Here, we demonstrate the effectiveness of a prostate-specific, locally delivered gene therapy for the targeted killing of prostate cells.

Methods: Using a degradable, poly(beta-amino ester) polymer, poly(butane diol diacrylate co amino pentanol) (C32), we developed a nanoparticulate system to deliver a diphtheria toxin suicide gene (DT-A) driven by a prostate specific promoter to cells. These C32/DT-A nanoparticles were directly injected to the normal prostate and to prostate tumors in mice.

Results: Nearly 50% of normal prostates showed a significant reduction in size, attributable to cellular apoptosis, whereas injection with naked DT-A-encoding DNA had little effect. Significant apoptosis was also observed in C32/DT-A injected prostate tumors. Importantly, no damage to surrounding tissue was observed.

Conclusions: These results suggest that local delivery of poly(beta-amino ester) polymer/ DT-A nanoparticles may have application in the treatment of BPH and prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • DNA / administration & dosage
  • DNA / genetics
  • Diphtheria Toxin / genetics*
  • Esters / administration & dosage
  • Genetic Therapy / methods*
  • In Situ Nick-End Labeling
  • Male
  • Mice
  • Mice, Transgenic
  • Nanoparticles / administration & dosage*
  • Peptide Fragments / genetics*
  • Plasmids / genetics
  • Polymers / administration & dosage
  • Promoter Regions, Genetic
  • Prostate-Specific Antigen / genetics*
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / therapy*
  • Statistics, Nonparametric

Substances

  • Diphtheria Toxin
  • Esters
  • Peptide Fragments
  • Polymers
  • diphtheria toxin fragment A
  • poly(beta-amino ester)
  • DNA
  • Prostate-Specific Antigen