Biomechanical effects of microbubbles: from radiosensitization to cell death

Ultrasound-stimulated microbubbles have been demonstrated to mechanically perturb cell membranes, resulting in the activation of biological signaling pathways that significantly enhance the effects of radiation. The underlying mechanism involves augmented ceramide production following both microbubble stimulation and irradiation, leading to rapid and extensive endothelial apoptosis and tumor cell death as a result of vascular collapse. Endothelial cells are particularly sensitive to ceramide-induced cell death due to an enriched presence of sphingomyelinase in their membranes. In tumors, this consequent rapid vascular shutdown translates to an overall increase in tumor responses to radiation treatments. This review summarizes the groundwork behind endothelial-based radiation enhancement with ultrasound-stimulated microbubbles, and presents ongoing research on the use of microbubbles as therapeutic agents in cancer therapy.