Ultrasound platform for diagnosis and targeted therapy – THERANOS

Novel concepts of nano medicine triggered the development of therapeutic agents of new generations with sizes ranging from nanometers to micrometers and including inventive functions. Local activation of such therapeutic components is an essential function, since it provides a longer therapeutic window and a higher therapeutic index in comparison to classical treatments such as chemotherapy. In addition local delivery minimizes secondary and side effects. Therefore active and targeted delivery opens new perspectives for therapy by providing a controlled release in space, time and on demand.
In recent years new promising possibilities for targeted drug and gene delivery have been discovered using ultrasound, gas microbubbles and nanoparticle drugs opening thus new therapeutic strategies. The use of this new therapeutic approach requires the design of new protocols for precise administration of active molecules (control and localization of the treated zones, real time imaging and monitoring). Although this new approach seems promising, it remains today difficult to bring it to a clinical level because of the lack of experimental tools that are essential for an in-vivo validation. For such a validation, it is necessary provide an ultrasound platform that is capable of generating ultrasound of medium intensities (few W/cm²), in a frequency range between 1 and 5 MHz to target a large spectrum of nanoparticles and microbubbles, and to perform imaging with a higher resolution (20 MHz and higher) in accordance with animal models used routinely (rats and mouse). The objective of the project is to develop an ultrasound theragnostic platform with dual function: therapy and diagnostic and to establish new and appropriate protocols for the activation of microbubbles and nanoparticles.
Although such a platform was considered unrealistic 10 years ago, new techniques of ultrasound transduction using cMUT technology (Capacitive Micromachined Ultrasonic Transducers) offer today a solution for such technological breakthrough. A cMUT based probe provides various possibilities to monitor the treated zones using either native imaging or contrast nonlinear imaging in addition to therapy. The project will allow us to reconsider the whole therapeutic procedure by exploiting the recent technological development possible with cMUT and to provide an optimized platform for preclinical validation.
The wafer bonding fabrication process has been chosen to develop cMUT probes in this project. The cMUT topology (membrane geometry and gap height) can be locally defined and matched to their role in the probe: low frequency therapy or high frequency (20 MHz) imaging. The platform will be based on a real time high resolution imaging system (15-50 MHz) for which a low frequency electronic card will be added for driving the acoustic emitters for therapy.
The experimental platform that will be developed in this project will make use of gas microbubbles and thermosensitive drug nanocarriers. The nanoparticles will be used as a drug carrier where the release is triggered from outside and on demand through focused ultrasound heating. Microbubbles will be used for imaging at high frequency and as a promoter of drug extravasation through the biological barriers and into tumors through the sonoporation process.
The validation of the final platform is also planned in order to evaluate the therapeutic efficacy and the image quality.