EGFP-EGF1-conjugated PLGA nanoparticles for targeted delivery of siRNA into injured brain microvascular endothelial cells for efficient RNA interference.
EGFP-EGF1-conjugated PLGA nanoparticles for targeted delivery of siRNA into injured brain microvascular endothelial cells for efficient RNA interference.
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EGFP-EGF1 缀合的 PLGA 纳米颗粒用于将 siRNA 靶向递送至受损脑微血管内皮细胞中以实现有效的 RNA 干扰
DOI：
10.1371/journal.pone.0060860
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Chen C;Mei H;Shi W;Deng J;Zhang B;Guo T;Wang H;Hu Y
脑微血管内皮细胞（BMEC）在多种病理生理条件下起着关键作用，因此损伤的内皮细胞是药物和/或基因治疗的重要靶点。RNA介导的基因沉默为治疗这些疾病提供了一种新的治疗方法，但主要的挑战是确保最小的毒性和靶向递送siRNA到受损的BMEC。受损的BMEC过度表达组织因子（TF），融合蛋白EGFP-EGF 1可以靶向于TF。在这项研究中，TNF-α（TNF-α）被选为刺激原代BMEC在体外产生损伤的内皮。将负载TF-siRNA的EGFP-EGF 1-PLGA纳米粒（ENPs）作为靶向递送至损伤的BMEC的新载体。然后，纳米颗粒产生针对TF的细胞内RNA干扰。我们比较了基于ENP的转染与NP介导的转染，并且我们的研究表明基于ENP的转染导致更有效的TF下调。我们的研究结果还表明，TF siRNA负载ENPs具有最小的毒性，转染后24小时几乎有96%的细胞存活，而基于脂质体的转染仅产生75%的细胞。因此，基于ENP的转染可用于对损伤的BMEC的有效siRNA转染和用于有效的RNA干扰（RNAi）。这种转染可以作为一种潜在的治疗疾病，如中风，动脉粥样硬化和癌症。
Injured endothelium is an important target for drug and/or gene therapy because brain microvascular endothelial cells (BMECs) play critical roles in various pathophysiological conditions. RNA-mediated gene silencing presents a new therapeutic approach for treating such diseases, but major challenge is to ensure minimal toxicity and target delivery of siRNA to injured BMECs. Injured BMECs overexpress tissue factor (TF), which the fusion protein EGFP-EGF1 could be targeted to. In this study, TNF alpha (TNF-α) was chosen as a stimulus for primary BMECs to produce injured endothelium in vitro. The EGFP-EGF1-PLGA nanoparticles (ENPs) with loaded TF-siRNA were used as a new carrier for targeted delivery to the injured BMECs. The nanoparticles then produced intracellular RNA interference against TF. We compared ENP-based transfections with NP-mediated transfections, and our studies show that the ENP-based transfections result in a more efficient downregulation of TF. Our findings also show that the TF siRNA-loaded ENPs had minimal toxicity, with almost 96% of the cells viable 24 h after transfection while Lipofectamine-based transfections resulted in only 75% of the cells. Therefore, ENP-based transfection could be used for efficient siRNA transfection to injured BMECs and for efficient RNA interference (RNAi). This transfection could serve as a potential treatment for diseases, such as stroke, atherosclerosis and cancer.
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影响因子：
4.8
作者：
Kim, I;Oh, JL;Koh, GY
通讯作者：
Koh, GY
影响因子：
10.8
作者：
Lu, W;Zhang, Y;Fu, SK
通讯作者：
Fu, SK
影响因子：
3.5
作者：
Mukerjee A;Shankardas J;Ranjan AP;Vishwanatha JK
通讯作者：
Vishwanatha JK
影响因子：
64.8
作者：
Castanotto, Daniela;Rossi, John J.
通讯作者：
Rossi, John J.
DOI：
10.1111/j.1538-7836.2009.03368.x
发表时间：
2009-07
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Mackman N
通讯作者：
Mackman N