| This work is focused on development of a technique for enhanced delivery of drugs and genes that utilizes interaction of nano- and microparticles with ultrasound radiation to produce cavitation selectively in tumors. The work is performed in phantoms, in vitro in cancer cells, and in vivo in nude mice bearing human tumors.; Studies in phantoms were focused on investigation of ultrasound-induced cavitation thresholds and the influence of polystyrene nanoparticles (100 and 280 nm in diameter and concentration up to 0.2% w/w) on cavitation threshold in water at the frequency of 20 kHz. These studies allowed estimating of optimal treatment parameters for enhancement of chemotherapy in mice in vivo .; In vitro studies of ultrasound-induced drug and gene delivery were performed at the frequencies of 1 and 3 MHz in seven human solid cancer cell lines. Optimization of ultrasound frequency, intensity, duty cycle, time of irradiation, and concentration of Optison (ultrasound contrast agent) for drug and gene delivery was performed in MCF7 breast cancer cells. Model drug delivery, associated cell death, and transfection 24 hours after the treatment were assessed in other cell lines using optimized parameters.; In animal studies, treatment parameters optimized in phantoms and in cells in vitro were investigated for delivery of model and real anti-cancer drugs in tumors. The experiments were performed in athymic nude mice bearing human colon KM20, breast MCF7, and prostate DU145 cancers. The studies demonstrated that improved delivery of the drug significantly decreased tumor volume and resulted in complete tumor regression at optimal irradiation conditions. (Abstract shortened by UMI.)... |
