RADIOLYSIS, PHOTOLYSIS AND SONOLYSIS OF CELLS AND THEIR CONSTITUENTS

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"Sonodynamic therapy is a promising new modality for cancer treatment based on the synergistic effect on cell killing by the combination of a drug (a sonosensitizer; usually a porphyrin) and ultrasound. The effectiveness of sonodynamic therapy has been demonstrated in cell studies and in tumor-bearing animals. The occurrence of acoustic cavitation is a necessary condition for the activation of sonosensitizers. Since the availability of cavitation nuclei in biological systems is very limited we have studied the feasibility of using stabilized microbubbles as potential sources of cavitation nuclei. Stabilized microbubbles are used widely for the enhancement of echo contrast in ultrasound imaging. We have investigated the mechanism of the ultrasound-dependent formation of hydrogen peroxide, hydroxyl radicals and hydrogen atoms ( these species are fingerprints for the occurrence of inertial cavitation in aqueous systems ) in the presence of clinically useful organic echo contrast agents such as Albunex and Levovist at concentrations comparable to those used in ultrasound imaging . In air-saturated solutions, the yields of hydrogen peroxide ( which can be a cell- killing agent above a certain concentration) are enhanced at ultrasound intensities above the cavitation threshold. In addition, the contrast agents themselves undergo combustion reactions in the cavitation bubbles as demonstrated by the formation of methyl radical which were identified by electron paramagnetic resonance methods. Possibly deleterious consequences of the formation of sonochemical intermediates may have to be assessed, particularly because some of the echo contrast agents have been shown to lower the cavitation threshold of diagnostic ultrasound . These results are also relevant with respect to the possible use of such microbubbles in gene therapy, due to the ability of stabilized microbubbles to release their content when exposed to diagnostic ultrasound. Unlike the microspheres formed from organic molecules, inorganic microspheres, Eccospheres, because of their stability and inert nature with respect to participation in free radical processes, appear to be suitable tools for enhancing the yields of aqueous sonochemical reactions."