Wu Sheng-Kai, Tsai Chia-Lin, Huang Yuexi, Hynynen Kullervo
Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Pharmaceutics. 2020 Dec 24;13(1):15. doi: 10.3390/pharmaceutics13010015.
The presence of blood-brain barrier (BBB) and/or blood-brain-tumor barriers (BBTB) is one of the main obstacles to effectively deliver therapeutics to our central nervous system (CNS); hence, the outcomes following treatment of malignant brain tumors remain unsatisfactory. Although some approaches regarding BBB disruption or drug modifications have been explored, none of them reach the criteria of success. Convention-enhanced delivery (CED) directly infuses drugs to the brain tumor and surrounding tumor infiltrating area over a long period of time using special catheters. Focused ultrasound (FUS) now provides a non-invasive method to achieve this goal via combining with systemically circulating microbubbles to locally enhance the vascular permeability. In this review, different approaches of delivering therapeutic agents to the brain tumors will be discussed as well as the characterization of BBB and BBTB. We also highlight the mechanism of FUS-induced BBB modulation and the current progress of this technology in both pre-clinical and clinical studies.
血脑屏障(BBB)和/或血脑肿瘤屏障(BBTB)的存在是有效向中枢神经系统(CNS)输送治疗药物的主要障碍之一;因此,恶性脑肿瘤的治疗效果仍然不尽人意。尽管已经探索了一些关于破坏血脑屏障或药物修饰的方法,但没有一种达到成功标准。传统增强递送(CED)使用特殊导管将药物长时间直接注入脑肿瘤及其周围的肿瘤浸润区域。聚焦超声(FUS)现在提供了一种非侵入性方法,通过与全身循环的微泡结合以局部增强血管通透性来实现这一目标。在本综述中,将讨论向脑肿瘤递送治疗药物的不同方法以及血脑屏障和血脑肿瘤屏障的特征。我们还重点介绍了FUS诱导血脑屏障调节的机制以及该技术在临床前和临床研究中的当前进展。