In vitro potentiation of doxorubicin by unseeded controlled non-inertial ultrasound cavitation.

Ultrasound-generated non-inertial cavitation has the ability to potentiate the therapeutic effects of cytotoxic drugs. We report a novel strategy to induce and regulate unseeded (without nucleation agents) non-inertial cavitation, where cavitation is initiated, monitored and regulated using a confocal ultrasound setup controlled by an instrumentation platform and a PC programmed feedback control loop. We demonstrate, using 4T1 murine mammary carcinoma as model cell line, that unseeded non-inertial cavitation potentiates the cytotoxicity of doxorubicin, one of the most potent drugs used in the treatment of solid tumors including breast cancer. Combined treatment with doxorubicin and unseeded non-inertial cavitation significantly reduced cell viability and proliferation at 72 h. A mechanistic study of the potential mechanisms of action of the combined treatment identified the presence of cavitation as required to enhance doxorubicin efficacy, but ruled out the influence of changes in doxorubicin uptake, temperature increase, hydroxyl radical production and nuclear membrane modifications on the treatment outcome. The developed strategy for the reproducible generation and maintenance of unseeded cavitation makes it an attractive method as potential preclinical and clinical treatment modality to locally potentiate doxorubicin.

Ultrasound-Induced Insulin Release as a Potential Novel Treatmentfor Type 2 Diabetes Mellitus.

Therapeutic ultrasound presents a potential novel treatment for type 2 diabetes mellitus that utilizes the non-invasive application of ultrasound energy to treat secretory defects in the earlier stages of the disease. Our previous studies have shown that ultrasound is capable of stimulating insulin release from pancreatic beta cells, safely and effectively. This study aims to both examine the calcium-dependent mechanisms of ultrasound-mediated insulin release from pancreatic beta cells using three complementary modalities - carbon fiber amperometry, ELISA studies, and Ca2+ fluorescence imaging - and to study the translational potential of therapeutic ultrasound using transgenic hyperglycemic mice for safety and efficacy studies.