Focused in vivo Delivery of Plasmid DNA to the Porcine Vascular Wall via Intravascular Ultrasound Destruction of Microbubbles
Focused in vivo Delivery of Plasmid DNA to the Porcine Vascular Wall via Intravascular Ultrasound Destruction of Microbubbles
复制标题
DOI：
10.1159/000258905
复制
发表时间：
2010-01-01
影响因子：
1.7
通讯作者：
Wamhoff, Brian R.
中科院分区：
文献类型：
--
作者：
Phillips, Linsey C.;Klibanov, Alexander L.;Wamhoff, Brian R.
背景：与药物洗脱支架相关的安全性问题激发了人们对血管成形术后替代血管治疗的兴趣。微泡造影剂已被证明在超声存在下增加体内基因转染。目的/方法：本研究的目的是确定血管内超声（IVUS）导管是否可以介导猪冠状动脉球囊成形术后质粒DNA从微泡载体转染到冠状动脉壁。结果：在质粒偶联微泡存在的情况下，只有经改良IVUS导管超声照射的细胞能显著表达转基因。猪左冠状动脉前降支行球囊血管成形术，然后在血管成形术部位注射和超声IVUS导管微泡。3天后，在接受微泡和IVUS的动脉中，与未接受IVUS的微泡组相比，转基因表达增加了约6.5倍。结论：本研究结果首次在体内证明了需要IVUS来增强基因从微泡载体到血管壁的转染。该技术可应用于药物和基因治疗，以减少血管再狭窄。版权所有(C) 2009 S. Karger AG，巴塞尔
Background: Safety concerns associated with drug-eluting stents have spurred interest in alternative vessel therapeutics following angioplasty. Microbubble contrast agents have been shown to increase gene transfection in vivo in the presence of ultrasound. Objectives/Methods: The purpose of this study was to determine whether an intravascular ultrasound (IVUS) catheter could mediate plasmid DNA transfection from microbubble carriers to the porcine coronary artery wall following balloon angioplasty. Results: In the presence of plasmid-coupled microbubbles in vitro only cells exposed to ultrasound from the modified IVUS catheter significantly expressed the transgene. A porcine left anterior descending coronary artery underwent balloon angioplasty followed by injection and insonation of microbubbles from the IVUS catheter at the site of angioplasty. After 3 days, an approximately 6.5-fold increase in transgene expression was observed in arteries that received microbubbles and IVUS compared to those that received microbubbles with no IVUS. Conclusions: The results of this study demonstrate for the first time that IVUS is required to enhance gene transfection from microbubble carriers to the vessel wall in vivo. This technology may be applied to both drug and gene therapy to reduce vessel restenosis. Copyright (C) 2009 S. Karger AG, Basel