Ultrasound guided site-specific gene delivery in prostate cancer

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DESCRIPTION (provided by applicant): This proposal aims at improving the efficiency and specificity of gene delivery in prostate cancer (PC) by using an innovative system consisting of ultrasound contrast agents, viral vectors and ultrasound waves. Additionally, this proposal aims at improving the response of prostate cancer to radiation therapy. Despite the progress of modern radiation techniques in largely improving the prognosis of patients with prostate adenocarcinoma, the maximum benefit that can be achieved with conventional radiation therapy has probably been reached. The impact of this proposal lies in the fact that a gene such as p130 significantly increases the percentage of apoptotic cells after 3- irradiation potentially improving the treatment of prostate cancer. Additionally, ultrasound contrast agents offer the advantage of targeted gene release, thereby improving its specificity. The impact of microbubbles on gene therapy is to protect the viral vectors from rapid degradation by the immune system thus allowing for intravenous injection rather than direct target organ injection. Ultrasound contrast agents (microbubbles) may be designed to serve as safe vehicles to encapsulate and deliver genetic materials. The gas filled microspheres effectively lower the energy threshold for cavitation. This allows diagnostic transducers operating within the energy levels mandated by the FDA to be used for drug/gene delivery. In the sonification zone the microbubbles undergo cavitation, destroying the bubbles and releasing their contents. Cavitation also creates small shockwaves that increase cell permeability. This has been shown to increase transcapillary passage of macromolecules or nanoshperes codelivered by the microbubbles in experimental animals. This proposal aims at improving the outcome of radiation therapy in prostate cancer. The outcome of these studies will demonstrate whether targeted p130 gene delivery is an effective adjuvant treatment in the therapy of prostate adenocarcinoma and whether its use could be directed at decreasing treatment-related morbidity. The results of these experiments will be the basis for future patient clinical trials. PUBLIC HEALTH RELEVANCE: This proposal aims at improving the efficiency and specificity of gene delivery in prostate cancer (PC) by using an innovative system consisting of ultrasound contrast agents, viral vectors and ultrasound waves. Additionally, this proposal aims at improving the response of prostate cancer to radiation therapy. Despite the progress of modern radiation techniques in largely improving the prognosis of patients with prostate adenocarcinoma, the maximum benefit that can be achieved with conventional radiation therapy has probably been reached. The impact of this proposal lies in the fact that a gene such as p130 significantly increases the percentage of apoptotic cells after 3- irradiation potentially improving the treatment of prostate cancer. Additionally, ultrasound contrast agents offer the advantage of targeted gene release, thereby improving its specificity. The impact of microbubbles on gene therapy is to protect the viral vectors from rapid degradation by the immune system thus allowing for intravenous injection rather than direct target organ injection. Additionally, viruses are non-specific. Ultrasound contrast agents (microbubbles) may be designed to serve as safe vehicles to encapsulate and deliver genetic materials. The gas filled microspheres effectively lower the energy threshold for cavitation. This allows diagnostic transducers operating within the energy levels mandated by the FDA to be used for drug/gene delivery. In the sonification zone the microbubbles undergo cavitation, destroying the bubbles and releasing their contents. Cavitation also creates small shockwaves that increase cell permeability. This has been shown to increase transcapillary passage of macromolecules or nanoshperes codelivered by the microbubbles in experimental animals. In conclusion, this proposal aims at improving the outcome of radiation therapy in prostate cancer. The outcome of these studies will demonstrate whether targeted p130 gene delivery is an effective adjuvant treatment in the therapy of prostate adenocarcinoma and whether its use could be directed at decreasing treatment-related morbidity. The results of these experiments will be the basis for future patient clinical trials.