Free Radical Intermediates in Sonodynamic Therapy

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Abstract
Current understanding of the mechanism of sonodynamic action (i.e. the ultrasound‐dependent enhancement of the cytotoxic action of certain drugs ‐ sonosensitizers) with potential applications for cancer therapy is presented. The experimental evidence suggests that sonosensitization is due to the chemical activation of sonosensitizers inside or in the close vicinity of hot collapsing cavitation bubbles to form sensitizer‐derived free radicals either by direct pyrolysis or due to reactions with ·H and ·OH radicals, formed by pyrolysis of water. These free radicals (mostly carbon‐centered) react with oxygen to form peroxyl and alkoxyl radicals. Unlike ·OH and ·H, which are also formed by pyrolysis inside cavitation bubbles, the reactivity of alkoxyl and peroxyl radicals with organic components dissolved in biological media is lower and hence have higher probability of reaching critical cellular sites. Sonodynamic therapy appears to be a promising modality for cancer treatment since ultrasound can penetrate deep within the tissue and can be focused in a small region of tumor to chemically activate relatively non‐toxic molecules (e.g. porphyrins) thus minimizing undesirable side effects.