Ultrasound imaging can spatially map small temperature changes resulting from hyperthermia. In our laboratory we release drugs from vehicles using mild hyperthermia. We have developed temperature-sensitive nanoparticles in which a drug is sequestered in a crystal at neutral pH and encapsulated in a lipid shell with a low melting point. After temperature-mediated release, the crystal is dissolved in a tumor or lysosome. By combining these particles with ultrasound, a large fraction of drug is delivered into tumors without systemic toxicity and we are achieving a complete response in local disease in a protocol that is not possible with existing agents. Combining this treatment with an immune adjuvant, we observe a powerful systemic anti-tumor response.
We are currently developing transducers and systems for real-time ultrasound thermometry based on 256-element arrays and a Verasonics platform. These transducers include a 2D therapeutic array that is confocally focused with an imaging array and provide the ability to steer the therapeutic beam in three dimensions.