Micro/nanoparticle-enabled ultrasound therapy of brain diseases

The structural complexity of the brain hinders the traditional treatment of brain diseases from achieving desirable outcomes, which urges the research and development of multiple alternatives. Rapid advances in materials science and nanomedicine have brought endless possibilities for the cure of brain diseases. The ideal depth of tissue penetration, precise and controllable therapeutic dose, and noninvasive nature of ultrasound (US) make it an unprecedented superiority in brain applications. Therefore, the US-stimulated multifunctional nanosystems have been extensively explored to meet the numerous requirements in the treatment of brain diseases. This article reviews and highlights recent advances in the utilization of US and micro/nanoparticles for the treatment of brain diseases, including common but intractable ones such as glioblastoma, ischemic stroke, Parkinson's disease, Alzheimer's disease, and so on. The composition and function of US-sensitive nanoplatforms based on different therapeutic principles are elaborated for different pathological mechanisms, and the validation of their in vitro and in vivo therapeutic effects are also introduced in detail. Finally, we discuss the biosafety issues closely related to future clinical translation, as well as some potential challenges and promising prospects.