摘要
超声联合微泡开启血脑屏障进行颅内药物递送是一种新的治疗脑胶质瘤方法,它具有无创、定点、高效促进药物透过血脑屏障的特点,可局部增加药物在病变组织的浓度,提高药物的疗效。在本研究中,我们利用内皮细胞和脑胶质瘤细胞构建了体外细胞血脑屏障模型,通过超声辐照,验证了超声联合微泡可以有效开启BBB,提高替莫唑胺纳米药物的BBB通透性,并显著增强纳米药物对脑胶质瘤细胞的杀伤活性。我们的研究提供了一种体外血脑屏障细胞模型的构建方法,并阐明了超声开启体外细胞血脑屏障增强脑胶质瘤细胞的治疗效果。
Drug delivery into brain tumor through ultrasound combined with microbubbles is a novel way to treat glioma. It has lots of advantages including its noninvasiveness, localization and high effectiveness to overcome blood brain barrier(BBB) and to enhance drugs into brain. In this study, we constructed an in vitro blood brain barrier model by using of b End.3 endothelial cells and C6 glioma cells. The effectiveness of nano-drugs across blood brain barrier under ultrasound irradiation was examined and the improved drug permeability was valuated. Significant more apoptotic tumor cells werefound in the ultrasound treated group, compared with control group. Our study provided a method to construct in vitro blood brain barrier model and evaluated the enhanced efficacy of nano-drugs via ultrasound combined with mi-crobubbles.
引文
[1]Pardridge WM.,et al.,Blood-brain barrier drug targeting:the future of brain drug development[J].Molecular Interventions(2003),3(2):90
[2]Carpenier Aal.,Clinical trial of blood-brain barrier disruption by pu lsed ultrasound[J].Sci Transl Med.2016 Jun 15;8(343):343re2.doi:10.1126/scitranslmed.aaf6086.
[3]Naik,P.,and Cucullo,L.(2012).In vitro blood–brain barrier models:current and perspective technologies.J.Pharm.Sci.101,1337–1354.doi:10.1002/jps.23022
[4]Cucullo,L.,Marchi,N.,Hossain,M.,and Janigro,D.(2011).Adynamic in vitro BBB model for the study of immune cell trafficking into the central nervous system.J.Cereb.Blood Flow Metab.31,767–777.doi:10.1038/jcbfm.2010.162.
[5]Mayer,C.R.,et al.,Ultrasound targeted microbubble destruction for drug and gene delivery[J].Expert Opin Drug Deliv,(1744-7593),2008.5(10):p.1121-1138.
[6]Choi,J.J.,et al.,Microbubble-size dependence of focused ultrasound-induced blood-brain barrier opening in mice in vivo[J].IEEE Trans Biomed Eng,2010.57(1):p.145-154.
[7]Chaichana KL,Establishing percent resection and residual volume t hresholds affecting survival andrecurrence for patients with newly diagnosed intracranial glioblastoma.Neuro Oncol.2014 Jan;16(1):113-22.doi:10.1093/neuonc/not137.Epub 2013 Nov 26.
[8]Reyderman L,Statkevich P,Thonoor CM,Patrick J,Batra VK,et al.(2004)Disposition and pharmacokinetics of temozolomide in rat.Xenobiotica 34:487-500