Physical Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Handb Exp Pharmacol. 2022;273:351-364. doi: 10.1007/164_2020_408.
For a chemotherapeutic agent to be effective, it must conquer the presence of blood-brain barrier (BBB), which limits the penetration of drugs into the brain. Tumours in the brain compromise the integrity of BBB and result in a highly heterogeneous vasculature, known as blood-brain tumour barrier (BBTB). In this chapter, we firstly highlight the cellular and molecular characteristics of the BBB and BBTB as well as the challenges aroused by BBB/BBTB for drug delivery. Secondly, we discuss the current strategies overcoming the challenges in invasive and non-invasive manners. Finally, we highlight the emerging strategy using focused ultrasound (FUS) with systemic microbubbles to transiently and reversibly enhance the permeability of these barriers for drug delivery.
为了使化疗药物有效,它必须克服血脑屏障(BBB)的存在,因为这限制了药物进入大脑。大脑中的肿瘤会破坏 BBB 的完整性,导致高度异质的血管,即血脑肿瘤屏障(BBTB)。在本章中,我们首先强调了 BBB 和 BBTB 的细胞和分子特征,以及 BBB/BBTB 对药物输送带来的挑战。其次,我们讨论了以侵入性和非侵入性方式克服这些挑战的现有策略。最后,我们强调了使用聚焦超声(FUS)联合全身微泡暂时和可逆地增强这些屏障通透性以进行药物输送的新兴策略。