Pinkiewicz Miłosz, Pinkiewicz Mateusz, Walecki Jerzy, Zaczyński Artur, Zawadzki Michał
Faculty of Medicine, Wroclaw Medical University, 50-367 Wrocław, Poland.
Department of Diagnostic Imaging, Mazowiecki Regional Hospital in Siedlce, 08-110 Siedlce, Poland.
Cancers (Basel). 2024 Jan 4;16(1):236. doi: 10.3390/cancers16010236.
The blood-brain barrier (BBB) poses a significant challenge to drug delivery for brain tumors, with most chemotherapeutics having limited permeability into non-malignant brain tissue and only restricted access to primary and metastatic brain cancers. Consequently, due to the drug's inability to effectively penetrate the BBB, outcomes following brain chemotherapy continue to be suboptimal. Several methods to open the BBB and obtain higher drug concentrations in tumors have been proposed, with the selection of the optimal method depending on the size of the targeted tumor volume, the chosen therapeutic agent, and individual patient characteristics. Herein, we aim to comprehensively describe osmotic disruption with intra-arterial drug administration, intrathecal/intraventricular administration, laser interstitial thermal therapy, convection-enhanced delivery, and ultrasound methods, including high-intensity focused and low-intensity ultrasound as well as tumor-treating fields. We explain the scientific concept behind each method, preclinical/clinical research, advantages and disadvantages, indications, and potential avenues for improvement. Given that each method has its limitations, it is unlikely that the future of BBB disruption will rely on a single method but rather on a synergistic effect of a combined approach. Disruption of the BBB with osmotic infusion or high-intensity focused ultrasound, followed by the intra-arterial delivery of drugs, is a promising approach. Real-time monitoring of drug delivery will be necessary for optimal results.
血脑屏障（BBB）对脑肿瘤的药物递送构成了重大挑战，大多数化疗药物对非恶性脑组织的渗透性有限，对原发性和转移性脑癌的作用也十分有限。因此，由于药物无法有效穿透血脑屏障，脑化疗后的治疗效果仍然不尽人意。已经提出了几种打开血脑屏障并在肿瘤中获得更高药物浓度的方法，最佳方法的选择取决于目标肿瘤体积的大小、所选的治疗药物以及个体患者的特征。在此，我们旨在全面描述动脉内给药、鞘内/脑室内给药、激光间质热疗、对流增强递送和超声方法（包括高强度聚焦超声和低强度超声以及肿瘤治疗电场）引起的渗透性破坏。我们解释了每种方法背后的科学概念、临床前/临床研究、优缺点、适应症以及潜在的改进途径。鉴于每种方法都有其局限性，血脑屏障破坏的未来不太可能依赖单一方法，而是依赖联合方法的协同效应。通过渗透灌注或高强度聚焦超声破坏血脑屏障，然后动脉内给药，是一种很有前景的方法。为了获得最佳效果，有必要对药物递送进行实时监测。
