Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA.
Adv Drug Deliv Rev. 2022 Dec;191:114583. doi: 10.1016/j.addr.2022.114583. Epub 2022 Oct 19.
The blood brain barrier (BBB) plays a critically important role in the regulation of central nervous system (CNS) homeostasis, but also represents a major limitation to treatments of brain pathologies. In recent years, focused ultrasound (FUS) in conjunction with gas-filled microbubble contrast agents has emerged as a powerful tool for transiently and non-invasively disrupting the BBB in a targeted and image-guided manner, allowing for localized delivery of drugs, genes, or other therapeutic agents. Beyond the delivery of known therapeutics, FUS-mediated BBB opening also demonstrates the potential for use in neuromodulation and the stimulation of a range of cell- and tissue-level physiological responses that may prove beneficial in disease contexts. Clinical trials investigating the safety and efficacy of FUS-mediated BBB opening are well underway, and offer promising non-surgical approaches to treatment of devastating pathologies. This article reviews a range of pre-clinical and clinical studies demonstrating the tremendous potential of FUS to fundamentally change the paradigm of treatment for CNS diseases.
血脑屏障(BBB)在中枢神经系统(CNS)内环境稳态的调节中起着至关重要的作用,但它也是治疗脑部疾病的主要限制因素。近年来,聚焦超声(FUS)联合充气体微泡造影剂已成为一种强大的工具,可通过靶向和图像引导的方式暂时、非侵入性地破坏 BBB,从而实现药物、基因或其他治疗剂的局部递送。除了递送已知的治疗药物外,FUS 介导的 BBB 开放还具有用于神经调节以及刺激一系列细胞和组织水平生理反应的潜力,这在疾病情况下可能是有益的。正在进行的临床试验调查了 FUS 介导的 BBB 开放的安全性和有效性,为破坏性疾病的治疗提供了有前途的非手术方法。本文综述了一系列临床前和临床研究,这些研究展示了 FUS 具有巨大的潜力,可以从根本上改变 CNS 疾病治疗的模式。