Men with prostate cancer, the most common cancer diagnosed in the US, are faced with making the difficult decision of choosing among different treatment options ranging from watchful waiting to chemotherapy, radiation therapy, or surgery. Some patients, however, because of age or other health issues, cannot tolerate existing therapies. In addition, current therapies are often accompanied by serious side effects that impact on the quality of life. Often these side effects are the result of damage to healthy tissues that are in close proximity to the prostate. Furthermore, many existing therapies treat the symptoms, but do not affect a permanent cure. Thus, there is a need for an improved therapy that is more effective, safer, and can be tolerated by more patients than existing treatments.
The utility of a cationic poly(b-amino ester)polymer, C32, for delivering DNA encoding a diphtheria toxin suicide gene (DT-A) to subcutaneous tumors derived from human prostate cancer cells in mice, resulting in tumor growth suppression. This study, as well as others, suggests the potential therapeutic value of targeting suicide gene expression to the enlarged prostate and to prostate tumor cells.
To further explore this potential, in this study, we used nanoparticles to deliver DT-A to normal prostate and prostate tumors in mice. In contrast to the earlier xenograft studies, this study tests efficacy of this potential therapy to kill cells within the prostate microenvironment. One advantage of suicide DNA-based therapy, as compared to other therapies, is that, in addition to delivering DNA to a specific site, cell-specific promoters can be used to regulate gene expression, resulting in the death of targeted cell populations, and the preservation of healthy tissue that is in close proximity to the targeted cells. In this study, a prostate-specific modified human PSA promoter, PSEBC [7], is used to regulate DT-A expression. The extensive apoptosis observed in prostate epithelial cells and prostate tumors, but not in surrounding tissues, following local injection of nanoparticle-delivered PSA/DT-A DNA suggests that this strategy may have application in the treatment of and prostate cancer.
