Ultrasound-mediated blood-brain barrier opening for targeted neurological drug delivery

Neurological disorders represent a devastating global health crisis, and the blood-brain barrier (BBB) remains a major obstacle for their treatment. Conventional strategies for BBB opening, including direct intracranial injection, osmotic disruption, receptor-mediated transcytosis, and nanoparticle carriers, often suffers from surgical invasiveness, systemic toxicity, poor biodistribution, and off-target effects. Ultrasound-mediated drug delivery has emerged as a revolutionary non-invasive technology for transient and targeted BBB opening, enabling enhanced penetration of therapeutic agents into the central nervous system. This review comprehensively summarizes the mechanisms underlying ultrasound-based delivery with focus on current delivery platforms including microbubble (MB)-assisted, nanoparticle-based, and MB-nanoparticle composite strategies. Furthermore, we highlight recent advances in the application of focused ultrasound (FUS) combined with MBs for the treatment of Alzheimer's disease, Parkinson's disease, and glioma. Finally, we discuss emerging technologies such as sonodynamic therapy and ultrasound-controlled magnetic nanorobots, while also addressing current challenges in this field. This review underscores the transformative potential of ultrasound-mediated drug delivery as a versatile platform for precision neurology. It also prospects future directions for advancing multidisciplinary research and clinical translation.