Targeted delivery of human VEGF gene via complexes of magnetic nanoparticle-adenoviral vectors enhanced cardiac regeneration.
Targeted delivery of human VEGF gene via complexes of magnetic nanoparticle-adenoviral vectors enhanced cardiac regeneration.
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DOI：
10.1371/journal.pone.0039490
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ma N
中科院分区：
文献类型：
--
作者：
Zhang Y;Li W;Ou L;Wang W;Delyagina E;Lux C;Sorg H;Riehemann K;Steinhoff G;Ma N
本研究评估了磁性纳米珠（MNBs）/腺病毒载体（Ad）编码的hVEGF基因（AdhVEGF）是否可以在外部磁场控制下在大鼠急性心肌梗死模型中再生缺血损伤的心脏。用磺基-NHS-LC-生物素接头将腺病毒载体缀合至MNB。在体外转导效率的MNBs/腺病毒编码的荧光素酶基因（Adluc）在人脐静脉内皮细胞（HUVECs）在磁场刺激下与单独的Adluc进行了比较。在体内，在大鼠急性心肌梗死（AMI）模型中，静脉注射MNB/AdhVEGF复合物，并采用心外膜磁体吸引循环中的MNB/AdhVEGF复合物。在体外实验中，与单独的Adluc相比，MNB/Adluc复合物在磁场下的转导效率高50倍。在体内，心外膜磁体有效地吸引MNB/AdhVEGF复合物，并导致在梗死心脏的缺血区中强烈的治疗基因表达。与其他MI治疗组相比，MI-M+/AdhVEGF组显著改善了左心室功能（p<0.05），4周后通过压力-容积环评估。此外，MI-M+/AdhVEGF组表现出比其他MI处理组更高的毛细血管和小动脉密度以及更低的胶原沉积（p<0.05）。磁性靶向增强转导效率并改善心脏功能。这种改善AMI基因治疗效果的新方法具有潜在的临床应用价值。
This study assessed the concept of whether delivery of magnetic nanobeads (MNBs)/adenoviral vectors (Ad)–encoded hVEGF gene (AdhVEGF) could regenerate ischaemically damaged hearts in a rat acute myocardial infarction model under the control of an external magnetic field. Adenoviral vectors were conjugated to MNBs with the Sulfo-NHS-LC-Biotin linker. In vitro transduction efficacy of MNBs/Ad–encoded luciferase gene (Adluc) was compared with Adluc alone in human umbilical vein endothelial cells (HUVECs) under magnetic field stimulation. In vivo, in a rat acute myocardial infarction (AMI) model, MNBs/AdhVEGF complexes were injected intravenously and an epicardial magnet was employed to attract the circulating MNBs/AdhVEGF complexes. In vitro, compared with Adluc alone, MNBs/Adluc complexes had a 50-fold higher transduction efficiency under the magnetic field. In vivo, epicardial magnet effectively attracted MNBs/AdhVEGF complexes and resulted in strong therapeutic gene expression in the ischemic zone of the infarcted heart. When compared to other MI-treated groups, the MI-M+/AdhVEGF group significantly improved left ventricular function (p<0.05) assessed by pressure-volume loops after 4 weeks. Also the MI-M+/AdhVEGF group exhibited higher capillary and arteriole density and lower collagen deposition than other MI-treated groups (p<0.05). Magnetic targeting enhances transduction efficiency and improves heart function. This novel method to improve gene therapy outcomes in AMI treatment offers the potential into clinical applications.
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影响因子：
3.7
作者：
Pandori, MW;Hobson, DA;Sano, T
通讯作者：
Sano, T
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20.1
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作者：
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通讯作者：
Schömig, A
影响因子：
19.7
作者：
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通讯作者：
Higgins, Charles B.