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. Copyright 2007 Wiley-Liss, Inc.
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. Copyright 2007 Wiley-Liss, Inc.
Authors: Yu-Hung Huang; Gregory T Zugates; Weidan Peng; David Holtz; Charles Dunton; Jordan J Green; Naushad Hossain; Michael R Chernick; Robert F Padera; Robert Langer; Daniel G Anderson; Janet A Sawicki Journal: Cancer Res Date: 2009-08-01 Impact factor: 12.701
Authors: Yu-Hung Huang; Yunhua Bao; Weidan Peng; Michael Goldberg; Kevin Love; David A Bumcrot; Geoffrey Cole; Robert Langer; Daniel G Anderson; Janet A Sawicki Journal: Proc Natl Acad Sci U S A Date: 2009-02-10 Impact factor: 11.205
Authors: Shayna L Showalter; Yu-Hung Huang; Agneszka Witkiewicz; Christina L Costantino; Charles J Yeo; Jordan J Green; Robert Langer; Daniel G Anderson; Janet A Sawicki; Jonathan R Brody Journal: Cancer Biol Ther Date: 2008-10-03 Impact factor: 4.742