Ultrasound activated nano-encapsulated targeted drug delivery and tumour cell poration.

INTRODUCTION: Recently, ultrasonic drug release has been a focus of many research groups for stimuli responsive drug release. It has been demonstrated that a focused ultrasound (FUS) beam rapidly increases the temperature at the focused tissue area. One potential mechanism of drug targeting is to utilize the induced heat to release or increase penetration of chemotherapy to cancer cells. The efficiency of targeted drug delivery may increase by using FUS beam in conjugation with nano--encapsulated drug carriers.The aim of this study is to investigate the effect of heat and ultrasound on the cellular uptake and therapeutic efficacy of an anticancer drug using Magnetic Resonance Imaging guided Focused Ultrasound (MRgFUS). MATERIALS AND METHODS: Human KB cells (CCL-17 cells) were seeded into 96-well plates and heat treated at 37-55°C for 2-10 min. Cell viability was determined using the colorimetric MTT assay. The cells were also subjected to MRgFUS and the degree of cell viability was determined. These experiments were conducted using an ExAblate 2000 system (InSightec, Haifa, Israel) and a GE 1.5 T MRI system, software release 15. RESULTS: We have observed a significant decrease in human KB cell viability due to heat (>41°C) in the presence of Doxorubicin (DOX), in comparison with DOX at normal culture temperature (37°C). The synergistic effect of heat with DOX may be explained by several mechanisms. One potential mechanism may be increased penetration of DOX to the cells during heating. In addition, we have shown that ultrasound induced cavitation causes cell necrosis. DISCUSSION AND FUTURE WORK: Further investigation is required to optimize the potential of MRgFUS to enhance cellular uptake of therapeutic agents. A novel delivery nano-vehicle developed by CapsuTech will be investigated with MRgFUS for its potential as a stimuli responsive delivery system.

Focused Ultrasound-Induced Suppression of Auditory Evoked Potentials in Vivo.

The goal of this study was to determine the feasibility of focused ultrasound-based neuromodulation affecting auditory evoked potentials (AEPs) in animals. Focused ultrasound-induced suppression of AEPs was performed in 22 rats and 5 pigs: Repetitive sounds were produced, and the induced AEPs were recorded before and repeatedly after FUS treatment of the auditory pathway. All treated animals exhibited a decrease in AEP amplitude post-treatment in contrast to animals undergoing the sham treatment. Suppression was weaker for rats treated at 2.3 W/cm2 (amplitudes decreased to 59.8 ± 3.3% of baseline) than rats treated at 4.6 W/cm2 (36.9 ± 7.5%, p <0.001). Amplitudes of the treated pigs decreased to 27.7 ± 5.9% of baseline. This effect lasted between 30 min and 1 mo in most treated animals. No evidence of heating during treatment or later brain damage/edema was observed. These results demonstrate the feasibility of inducing significant neuromodulation with non-thermal, non-invasive, reversible focused ultrasound. The long recovery times may have clinical implications.