Polymeric Nanoparticles for Sustained Down-Regulation of Annexin A2 Inhibit Prostate Tumor Growth
Polymeric Nanoparticles for Sustained Down-Regulation of Annexin A2 Inhibit Prostate Tumor Growth
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DOI：
10.1166/jnn.2009.028
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发表时间：
2009-05-01
影响因子：
--
通讯作者：
Vishwanatha, Jamboor K.
中科院分区：
文献类型：
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作者：
Braden, Arthur R.;Kafka, Michael I.;Vishwanatha, Jamboor K.
前列腺癌是西方男性中最常诊断的癌症，也是癌症相关死亡的第二大原因。在前列腺上皮内瘤变中，膜联蛋白A2表达不存在，然而，在雄激素依赖性丧失后，膜联蛋白A2随后过表达。重新获得膜联蛋白A2的调节控制提供了治疗激素难治性前列腺癌的一种治疗手段。为了重新获得对异常膜联蛋白A2表达的控制，我们配制了载有pDrive-sh AnxA2质粒DNA的聚乳酸-共-乙交酯（PLGA）纳米颗粒。这些纳米颗粒能够持续细胞内递送pDrive-sh AnxA2质粒DNA载体，用于长期siRNA介导的膜联蛋白A2的下调。肿瘤内施用pDrive-sh AnxA2负载的纳米颗粒至裸鼠中的异种移植前列腺肿瘤显示肿瘤生长的总体降低。肿瘤生长的减少是通过肿瘤块内膜联蛋白A2和VEGF mRNA和蛋白水平的降低。空白纳米颗粒的给药表明在mRNA或蛋白质水平上肿瘤生长或膜联蛋白A2和VEGF没有改变。我们的研究结果表明，使用缓释聚合物纳米颗粒下调膜联蛋白A2的表达可能作为一种有效的辅助治疗前列腺癌的选择。
Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer related death in Western men. In prostate intraepithelial neoplasia annexin A2 expression is absent however upon loss of androgen dependence annexin A2 is subsequently over-expressed. Regaining regulatory control of annexin A2 presents a means of therapy in the treatment of hormone refractory prostate cancers. In an effort to regain control of aberrant annexin A2 expression we have formulated poly lactide-co-glycolide (PLGA) nanoparticles loaded with pDrive-sh AnxA2 plasmid DNA. These nanoparticles are capable of sustained intracellular delivery of pDrive-sh AnxA2 plasmid DNA vector for long term siRNA mediated down-regulation of annexin A2. Intra-tumoral administration of pDrive-sh AnxA2 loaded nanoparticles to xenograft prostate tumors in nude mice demonstrates an overall decrease in tumor growth. The decrease in tumor growth is through a reduction of annexin A2 and VEGF mRNA and protein levels within the tumor mass. Administration of blank nanoparticles demonstrated no alteration in tumor growth or annexin A2 and VEGF at either the mRNA or protein levels. Our findings suggest that the use of sustained-release polymeric nanoparticles for down-regulation of annexin A2 expression may serve as an effective adjuvant treatment option for prostate cancer.