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首页> 外文期刊>Journal of pharmaceutical sciences. >Disposition and gene expression characteristics in solid tumors and skeletal muscle after direct injection of naked plasmid DNA in mice.
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Disposition and gene expression characteristics in solid tumors and skeletal muscle after direct injection of naked plasmid DNA in mice.

机译：直接在小鼠中注射裸质粒DNA后在实体瘤和骨骼肌中的分布和基因表达特征。

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摘要

Previous studies have suggested that direct injection of naked plasmid DNA (pDNA) into solid tumors can be a useful method for in vivo gene transfer into tumor cells. To gain more insight into this approach, we studied the disposition and gene expression characteristics of naked pDNA after intratumoral injection by direct comparison with those after intramuscular injection in mice. pDNA encoding reporter genes were directly injected into subcutaneous solid tumor models and skeletal muscles. Biodistribution studies using radiolabeled pDNA showed that the elimination of pDNA from the injection site was relatively fast and a part of the pDNA was absorbed from the lymphatic system after both local injections. Confocal microscopic studies using fluorescein-labeled pDNA demonstrated that pDNA distributed efficiently throughout the muscle tissue whereas pDNA localization in the tumor tissue was restricted. Characterization of gene expression clarified the variation in expression level between tumor preparations and some factors affecting the expression level in the tumor. Reporter gene expression was significantly inhibited by simultaneous administration of some polyanions in both cases, suggesting that a specific mechanism may be involved in the naked pDNA uptake by muscle and tumor cells. These findings provide useful information for direct naked pDNA delivery into solid tumors.
机译：先前的研究表明，将裸质粒DNA（pDNA）直接注射到实体瘤中可能是将体内基因转移到肿瘤细胞中的有用方法。为了更深入地了解这种方法，我们通过与小鼠肌肉注射后的直接比较研究了肿瘤内注射后裸露的pDNA的配置和基因表达特征。将编码报告基因的pDNA直接注入皮下实体瘤模型和骨骼肌中。使用放射性标记的pDNA进行的生物分布研究表明，在两次局部注射后，从注射部位清除pDNA的速度相对较快，一部分pDNA被淋巴系统吸收。使用荧光素标记的pDNA的共聚焦显微镜研究表明，pDNA在整个肌肉组织中有效分布，而pDNA在肿瘤组织中的定位受到限制。基因表达的特征阐明了肿瘤制剂之间表达水平的差异以及一些影响肿瘤表达水平的因素。在两种情况下，同时施用一些聚阴离子均显着抑制了报告基因的表达，这表明特定的机制可能与肌肉和肿瘤细胞裸露的pDNA吸收有关。这些发现为将裸露的pDNA直接递送到实体瘤中提供了有用的信息。

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