Radiolysis, Photolysis and Sonolysis of Cells and their

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Summary of work: Sonodynamic therapy is a promising new modality for cancer treatment based on the synergistic effects of cell killing by a combination of sonosensitzer and ultrasound. Ultrasound can penetrate deeply into tissue and can be focused in a small region of tumor to activate non-toxic molecules (e.g. porphyrins ) thus minimizing undesirable side effects. The experimental evidence suggests that sonosensitization is due to the chemical activation of sonosensitizers inside or in close vicinity of hot collapsing cavitation bubbles to form sensitizer-derived radicals either by direct pyrolysis of the sensitizer at the water-gas interface or due to the reactions of hydrogen atoms and hydroxyl radicals formed by the pyrolysis of water. The free radicals derived from the sonosensitizer (mostly carbon-centered) react with oxygen to form peroxyl and alkoxyl radicals. Unlike OH radicals and H atoms which are formed by pyrolysis inside cavitation bubbles, the reactivity of alkoxyl and peroxyl radicals with organic compounds in biological media is much lower and hence they have a higher probability of reaching critical cellular sites. It is known that the ultrasound frequency affects the number of radicals that can be produced during sonolysis and the efficiency of sonodynamic therapy. A major limitation in determining effects of ultrasound frequency in sonochemistry due to cavitation is the absence of a relationship between the energy supplied to the system and the energy converted by the cavitation process into a sonochemical effect. Recently we have found a frequency effect which is independent of the energy supplied to the system. Spin trapping of secondary carbon radicals with 3,5-dibromo-4-nitrosobenzenesulfonic acid and electron paramagnetic resonance have been used to determine the relative ability of 2 non-volatile surfactants [sodium 1-pentanesulfonic acid (SPSo) and sodium dodecyl sulfate (SDS)] to scavenge H atoms and OH radicals at the gas/solution interface of cavitation bubbles at 3 frequencies ( 47, 354 and 1057 kHz ). At specific bulk concentrations the surfactants reach a limiting plateau value in radical scavenging ability. At 354 and 47 kHz the magnitude of this plateau was greater for SPSo than for SDS. However at 1057 kHz no difference in the plateau values was observed.. Thus at the plateau concentrations the relative ability of these n-alkyl chain surfactants to scavenge radicals at the gas/solution interface of cavitation bubbles depends on the ultrasound frequency but is independent of the ultrasound intensity. These observations can be explained in terms the effect of the rate of change of the surface area of "high energy stable cavitation bubbles" at different ultrasound frequencies on the ability of surfactants to accumulate at the gas/solution interface of cavitation bubbles.