The principal objective of the Sound Pharma project is to increase the therapeutic index of potent, often toxic treatments through personalized image-guided treatment, which ultimately decreases adverse effects of drugs by better controlling the pharmacokinetics (PK) and pharmacodynamics (PD) of therapy. For local disease, exogenous energy will be used to to release drugs entrapped within nanoparticles circulating through the tumor. This will be achieved via a combination of Focused Ultrasound, and drug nanocarriers that are sensitive to bio-effects of ultrasound.The drug ¿magic bullet¿ is at the heart of Pharma¿s business model. However, targeted drug delivery is increasingly being recognized as a key limiting factor of drug efficacy. Nanotechnologies are providing new formulations as well as novel methods for targeting. The combination of nanotechnologies and external triggering will provide novel technologies to achieve spatio-temporal control of drug delivery. The effect of ultrasound in tissue allows the local deposition of drugs from nanocarriers circulating in the blood, and/or their local activation. This is the case when using nanocarriers sensitive to mechanical forces and/or to small temperature elevations. Extravasation and membrane permeability are also enhanced by ultrasound. This new field of Image Guided Drug Delivery opens up opportunities for Pharma to expand applications for their existing small drugs (e.g. doxorubicin, cisplatin, irinitecan) in cancer by altered pharmacokinetics. This project intends to develop new focused ultrasound methods for drug delivery, based on local control of temperature and pressure, and by monitoring and validating intracellular uptake in real time using optical and MRI methods. The developed FUS methods will be applied to treatment of liver cancer using nanocarriers containing well known chemotherapeutica, via animal models, as well as in the clinic.