Translation of focused ultrasound for blood-brain barrier opening in glioma

• Published in: Journal of controlled release 2022-05, Vol.345, p.443-463
• Main Authors: Brighi, Caterina, Salimova, Ekaterina, de Veer, Michael, Puttick, Simon, Egan, Gary
• Format: Article
• Language: English
• Subjects: Blood-brain barrier; Drug delivery; Glioblastoma; Immunotherapy; Preclinical focused ultrasound; Sterile inflammation
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2022.03.035

Survival outcomes for patients with glioblastoma multiforme (GBM) have remained poor for the past 15 years, reflecting a clear challenge in the development of more effective treatment strategies. The efficacy of systemic therapies for GBM is greatly limited by the presence of the blood-brain barrier (BBB), which prevents drug penetration and accumulation in regions of infiltrative tumour, as represented in a consistent portion of GBM lesions. Focused ultrasound (FUS) – a technique that uses low-frequency ultrasound waves to induce targeted temporary disruption of the BBB – promises to improve survival outcomes by enhancing drug delivery and accumulation to infiltrating tumour regions. In this review we discuss the current state of preclinical investigations using FUS to enhance delivery of systemic therapies to intracranial neoplasms. We highlight critical methodological inconsistencies that are hampering clinical translation of FUS and we provide guiding principles for future preclinical studies. Particularly, we focus our attention on the importance of the selection of clinically relevant animal models and to the standardization of methods for FUS delivery, which will be paramount to the successful clinical translation of this promising technology for treatment in GBM patients. We also discuss how preclinical FUS research can benefit the development of GBM immunotherapies. [Display omitted] •More clinically relevant models of glioma are needed for preclinical FUS studies.•Methods standardization for FUS delivery is required for clinical translation.•Preclinical FUS evaluations should use clinically translatable in vivo imaging methods.•FUS can induce a beneficial anti-tumour immune response in glioblastoma.•FUS can be used to allow delivery of targeted immunotherapies in glioblastoma.