Method of using high-frequency sound waves

A high-frequency sound wave mediated therapeutic method, comprising:

• administering a plurality of acoustically active particles and a separate therapeutic agent to a subject, the plurality of acoustically active particles comprising a diameter in the range of 3 to 10 μm and a circularity of <0.9, individual acoustically active particles formed by mixing a gaseous component and an oil component, the oil component comprising a vaporous component configured to diffuse into the gaseous component so as to transiently increase the size thereof;
• applying a first application of high-frequency sound waves comprising a first frequency of about 2-10 MHz and a mechanical index of less than 0.4 to a region of interest within the subject to activate a phase shift of the vaporous component, the first application of high-frequency sound waves configured such that the gaseous component of the acoustically active particles are enlarged by the vaporous component to form enlarged particles which are trapped at the region of interest;
• and
• applying a second application of high-frequency sound waves comprising a second frequency of about 200-1000 kHz and a mechanical index of less than 0.4 to the region of interest to oscillate the enlarged particles thereby facilitating extravasation of the separate therapeutic agent to a tissue compartment of the region of interest, the second application applied after the first application
• wherein the gaseous component and the oil component have opposite surface charges and form the acoustically active particles via attractive electrostatic interactions,
• wherein the first frequency is different from the second frequency,
• wherein the second application is pulsed, and
• wherein the separate therapeutic agent is selected from the group consisting of a gene therapy drug, a chemotherapeutic, an immunotherapeutic agent, and an angiogenesis stimulating drug.