A novel dual-targeted ultrasound contrast agent provides improvement of gene delivery efficiency in vitro
A novel dual-targeted ultrasound contrast agent provides improvement of gene delivery efficiency in vitro
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一种新型双靶向超声造影剂可提高体外基因传递效率
DOI：
10.1007/s13277-015-4681-7
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Yan Fei
中科院分区：
文献类型：
--
作者：
Xu Jinfeng;Zeng Xinxin;Liu Yingying;Luo Hui;Wei Zhanghong;Liu Huiyu;Zhou Yuli;Zheng Hairong;Zhou Jie;Tan Guanghong;Yan Fei
超声靶向微泡破坏(UTMD)已成为肿瘤治疗应用中的一种新的基因/药物传递方法。然而，UTMD介导的基因转染率仍不理想。在这里，我们介绍了IRGD/CCR2双靶向阳离子微泡(MBiRGD/CCR2)，它被PEI-600修饰并包被IRGD多肽和抗CCR-2抗体。结果表明，MBiRGD/CCR2的表面Zeta电位为25.83 ± 1.57 mV，稳定性较好。体外实验表明，MBiRGD/CCR2与bEnd.3和MCF7细胞的结合效率均高于IRGD或CCR2单靶向阳离子微泡(MBiRGDor MBCCR2)(P<； 均为0.05)。琼脂糖凝胶电泳分析表明，MBiRGD/CCR2能有效负载pGPU6/GFP/Neo-shAKT2质粒DNA。与单纯MBS或包括MBiRGD和MBCCR2的单靶向阳离子MBS(均为P<； 0.05)相比，双靶向阳离子MBiRGD/CCR2组在超声照射下具有更高的基因转染率。结果表明，双靶向阳离子MBiRGD/CCR2作为超声成像探针用于肿瘤基因治疗具有潜在的应用价值。
Ultrasound-targeted microbubble destruction (UTMD) has become a novel gene/drug delivery method in cancer therapeutic application. However, the gene transfection efficiency mediated by UTMD is still unsatisfactory. Here, we introduced iRGD/CCR2 dual-targeted cationic microbubbles (MBiRGD/CCR2) which was modified with PEI-600 and coated with iRGD peptides and anti-CCR-2 antibodies. It showed that MBiRGD/CCR2had a 25.83 ± 1.57 mV surface zeta potential and good stability. The experiments in vitro showed MBiRGD/CCR2had higher binding efficiency with both bEnd.3 cells and MCF-7 cells than that of iRGD or CCR2 single-targeted cationic microbubbles (MBiRGDor MBCCR2) (P< 0.05 for both). Agarose gel electrophoresis assay showed that MBiRGD/CCR2can effectively load pGPU6/GFP/Neo-shAKT2 plasmid DNA. Compared with the plain MBs (MBcontrol) or single-targeted cationic MBs including MBiRGDand MBCCR2(P< 0.05 for all), the dual-targeted cationic MBiRGD/CCR2groups had higher gene transfection efficiency under US exposure. It showed that the dual-targeted cationic MBiRGD/CCR2has a potential value to be used as an ultrasound imaging probe for ultrasound image-guided tumor gene therapy.
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影响因子：
8
作者：
Knuefermann, C;Lu, Y;Fan, Z
通讯作者：
Fan, Z
影响因子：
9.7
作者：
Chandrashekhar, Chittimalla;Pons, Benedicte;Zuber, Guy
通讯作者：
Zuber, Guy
影响因子：
4
作者：
Wong, Kwok-Kin;Engelman, Jeffrey A.;Cantley, Lewis C.
通讯作者：
Cantley, Lewis C.
影响因子：
2.9
作者：
Yueh-Hsun Chuang;Yu-Hsin Wang;Tien-Kuei Chang;Ching-Jung Lin;Pai-Chi Li
通讯作者：
Yueh-Hsun Chuang;Yu-Hsin Wang;Tien-Kuei Chang;Ching-Jung Lin;Pai-Chi Li
影响因子：
6
作者：
M. Wolf;I. Clark‐Lewis;C. Buri;H. Langen;M. Lis;L. Mazzucchelli
通讯作者：
M. Wolf;I. Clark‐Lewis;C. Buri;H. Langen;M. Lis;L. Mazzucchelli