Intravascular ultrasound detection and delivery of molecularly targeted microbubbles for gene delivery.
Intravascular ultrasound detection and delivery of molecularly targeted microbubbles for gene delivery.
复制标题
用于基因传递的分子靶向微泡的血管内超声检测和传递。
DOI：
10.1109/tuffc.2012.2359
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Hossack,JohnA
中科院分区：
文献类型：
--
作者：
Phillips,LinseyC;Klibanov,AlexanderL;Wamhoff,BrianR;Hossack,JohnA
我们正在研究基于微泡的靶向药物递送和血管内超声（IVUS）成像的组合作为一种潜在的治疗方法，以减少动脉粥样硬化冠状动脉支架置入后再狭窄的发生率。这些研究的目的是确定IVUS是否可用于检测靶向微泡并通过靶向增强药物/基因递送。用细胞因子IL-1β刺激静止的血管平滑肌细胞（SMC），诱导炎性细胞表面标志物血管细胞粘附分子1（VCAM-1）的表达。将分子靶向的（VCAM-1 Ab或IgG对照Ab）荧光标记的微泡与表达绿色荧光蛋白（GFP，pMax-GFP）的质粒DNA缀合，并在流动下暴露于发炎的SMC以测量与对照微泡相比的粘附。使用改良的IVUS导管在200 kPa下产生1.5 MHz超声进行基因递送。使用IVUS导管和扫描仪检测培养和流动室中发炎SMC的粘附微泡。VCAM-1靶向微泡增强粘附发炎SMC 100倍以上的非靶向微泡。与未发炎的SMC相比，VCAM-1靶向微泡显示出对IL-1β处理的细胞的粘附增加了7.9倍。与非靶向微泡相比，靶向微泡与聚焦的2.54厘米（1英寸）直径1 MHz换能器结合使用时，质粒DNA转染增加了5.5倍，并且还增强了1.5 MHz下改良IVUS换能器的转染。靶向微泡（密度为3 × 104个微泡/mm 2）使IVUS图像强度比非微泡涂层表面增加13.2 dB。从修改后的IVUS换能器的微泡破裂导致图像强度降低53%。总之，这些结果表明，IVUS可用于检测炎症脉管系统的靶向微泡，随后局部递送基因/药物。
We are investigating the combination of microbubble-based targeted drug delivery and intravascular ultrasound (IVUS) imaging as a potential therapy to reduce incidence of restenosis following stent placement in atherosclerotic coronary arteries. The goal of these studies was to determine whether IVUS could be used to detect targeted microbubbles and enhance drug/gene delivery through targeting. Quiescent vascular smooth muscle cells (SMCs) were stimulated with cytokine IL-1β to induce the inflammatory cell surface marker vascular cell adhesion molecule 1 (VCAM-1). Molecular-targeted (VCAM-1 Ab or IgG control Ab), fluorescent-labeled microbubbles were conjugated with plasmid DNA expressing green fluorescent protein (GFP, pMax-GFP) and exposed to the inflamed SMCs under flow to measure adhesion compared with control microbubbles. Gene delivery was performed using a modified IVUS catheter to generate 1.5-MHz ultrasound at 200 kPa. Detection of adherent microbubbles to inflamed SMCs in culture and flow chambers was measured using an IVUS catheter and scanner. VCAM-1-targeted microbubbles enhanced adhesion to inflamed SMCs 100-fold over nontargeted microbubbles. Compared with noninflamed SMCs, VCAM-1-targeted microbubbles exhibited a 7.9-fold increase in adhesion to IL-1β-treated cells. Targeted microbubbles resulted in a 5.5-fold increase in plasmid DNA transfection over nontargeted microbubbles in conjunction with a focused 2.54-cm (1-in) diameter 1-MHz transducer and also enhanced transfection by the modified IVUS transducer at 1.5 MHz. Targeted microbubbles (at a density of 3 × 104microbubbles/mm2) increased IVUS image intensity 13.2 dB over non-microbubble-coated surfaces. Rupture of microbubbles from the modified IVUS transducer resulted in a 53% reduction in image intensity. Taken together, these results indicate that IVUS may be used to detect targeted microbubbles to inflamed vasculature and subsequently deliver a gene/drug locally.
使用 ECIS 监测细胞-ECM 相互作用
DOI：
--
发表时间：
2005
期刊：
影响因子：
--
作者：
C. Keese;J. Wegener;I. Giaever
通讯作者：
I. Giaever