Immunomodulation and targeted drug delivery with high intensity focused ultrasound (HIFU): Principles and mechanisms

High intensity focused ultrasound (HIFU) is a non-invasive and non-ionizing sonic energy-based therapeutic technology for inducing thermal and non-thermal effects in tissues. Depending on the parameters, HIFU can ablate tissues by heating them to >55 °C to induce denaturation and coagulative necrosis, improve radio- and chemo-sensitizations and local drug delivery from nanoparticles at moderate hyperthermia (∼41-43 °C), and mechanically fragment cells using acoustic cavitation (also known as histotripsy). HIFU has already emerged as an attractive modality for treating human & veterinary cancers, infectious diseases, and neuromodulation. Herein, we comprehensively review the role of HIFU in enhancing drug delivery and immunomodulation in soft and calcified tissues. Specifically, the ability of HIFU to improve adjuvant treatments from various classes of therapeutic agents are described. These crucial insights highlight the opportunities and challenges of HIFU technology and its potential to support new clinical trials and translation to patients.