Studies on neutral, cationic and biotinylated cationic microbubbles in enhancing ultrasound-mediated gene delivery in vitro and in vivo
Studies on neutral, cationic and biotinylated cationic microbubbles in enhancing ultrasound-mediated gene delivery in vitro and in vivo
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DOI：
10.1016/j.actbio.2011.09.010
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发表时间：
2012-03-01
影响因子：
9.7
通讯作者：
McHale, Anthony P.
中科院分区：
文献类型：
--
作者：
Nomikou, Nikolitsa;Tiwari, Poonam;McHale, Anthony P.
超声介导的基因转移正在成为促进靶向基因表达的一种实用手段，并在存在外源添加的微泡时显著增强。本研究探讨了微泡表面修饰对其与质粒DNA和靶细胞相互作用的影响，以及这些相互作用在超声介导的基因转移方面的功能后果。比较了聚乙二醇稳定的、具有中性(SDM201)、阳离子(SDM202)和生物素化阳离子(SDM302)表面的脂壳微泡与荧光素酶编码报告质粒DNA以及体外与靶细胞相互作用的能力。结果表明，生物素化的阳离子微泡>；阳离子微泡>；中性微泡，就其与靶细胞的相互作用和增强超声介导的基因转移的能力而言，特别是在低微泡浓度下。两个阳离子微泡上净正电荷的存在促进了微泡-核酸复合体的形成，尽管复合体在加入靶细胞之前预先形成抑制了微泡与体外靶细胞之间的相互作用。这些发现对微泡增强超声介导的基因转移的潜在的体外或体外治疗应用的影响被讨论。这三种微泡制剂都可以用来促进体内的基因转移，并讨论了使用阳离子微泡进行靶向基因传递的潜在优势。皇冠版权(C)2011由爱思唯尔有限公司代表Acta Materialia Inc.出版。保留所有权利。
Ultrasound-mediated gene transfer is emerging as a practical means of facilitating targeted gene expression and is significantly enhanced in the presence of exogenously added microbubbles. This study explores the influence of microbubble surface modifications on their interaction with plasmid DNA and target cells, and the functional consequences of those interactions in terms of ultrasound-mediated gene transfer. Polyethylene glycol-stabilized, lipid-shelled microbubbles with neutral (SDM201), cationic (SDM202) and biotinylated cationic (SDM302) surfaces were compared in terms of their abilities to interact with a luciferase-encoding reporter plasmid DNA and with target cells in vitro. The results demonstrate that the biotinylated cationic microbubble > cationic microbubble > neutral microbubble, in terms of their abilities to interact with target cells and to enhance ultrasound-mediated gene transfer, particularly at low microbubble concentration. The presence of a net positive charge on both cationic microbubbles promoted the formation of microbubble-nucleic acid complexes, although preformation of the complexes prior to addition to target cells inhibited the interaction between the microbubbles and target cells in vitro. The impact of these findings on potential in vitro or ex vivo therapeutic applications of microbubble-enhanced ultrasound-mediated gene transfer is discussed. All three microbubble preparations could be used to facilitate gene transfer in vivo and the potential advantages associated with the use of the cationic microbubbles for targeted gene delivery are discussed. Crown Copyright (C) 2011 Published by Elsevier Ltd. on behalf of Acta Materialia Inc. All rights reserved.