Free Radical Intermediates in Sonodynamic Therapy

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.

Cytotoxic Effect of Protoporphyrin IX to Human Leukemia U937 Cells under Ultrasonic Irradiation

“…It is known that some ROS products derived from the sonosensitizer during sonodynamic treatment process, and they are important factors of cell death regulation [20,30,31]. In our experiment, the generation of intracellular ROS was detected.…”

Engineered Porphyrin Loaded Core-Shell Nanoparticles for Selective Sonodynamic Anticancer Treatment

“…These species are than able to damage cells by peroxidizing lipids and disrupting DNA and proteins, but also to exert signaling functions and modulate gene transcription, thereby resulting in cellular dysfunction and apoptosis [25]. On this topic, we first introduced the use of shock wave (SW) to trigger sonosensitizer's cytotoxicity, since pulsed ultrasound generates significantly less thermal effect than continuous ultrasound [26].…”

Estimation of sonodynamic treatment region with sonochemiluminescence in gel phantom

“…1,2) Sonodynamic treatment is another type of ultrasonic cancer treatment generating reactive oxygen species (ROS) by combining acoustic cavitation and a sensitizer. [3][4][5][6][7][8] When a microbubble is subjected to ultrasound at its resonant frequency, its oscillation amplitude increases to an extreme. This is followed by its catastrophic collapse, at which the gas inside it may receive virtually adiabatic compression causing a temperature increase to thousands of degrees centigrade.…”