Progress and potential of nanobubbles for ultrasound-mediated drug delivery

Despite much progress, nanomedicine-based drug therapies in oncology remain limited by systemic toxicity and insufficient particle accumulation in the tumor. To address these barriers, formulations responsive to external physical stimuli have emerged. One most promising system is the ultrasound stimulation of drug-loaded, gas-core particles (bubbles). Ultrasound induces bubble cavitation for cell and tissue permeabilization, triggers on-demand drug release, and provides opportunities for real-time imaging of delivery.

Here, we focus on shell-stabilized, gas-core nanoparticles (also termed nanobubbles or ultrafine bubbles) and their role in ultrasound-mediated therapeutic delivery to tumors. This review frames the advantages of nanobubbles within the ongoing deficits in nanomedicine, describes mechanisms of ultrasound-mediated therapy, and details formulation techniques for nanobubble delivery systems. It then highlights the past decade of research in nanobubble-facilitated drug delivery for cancer therapy and anticipates new directions in the field.

Nanobubble ultrasound contrast agents offer a spatiotemporally triggerable therapeutic coupled with a safe, accessible imaging modality. Nanobubbles can be loaded with diverse therapeutic cargoes to treat disease and overcome numerous barriers limiting delivery to solid tumors. Close attention to formulation, characterization methods, acoustic testing parameters, and the biological mechanisms of nanobubble delivery will facilitate preclinical research toward clinical adoption.