An immobilized nanoparticle-based platform for efficient gene knockdown of targeted cells in the circulation
An immobilized nanoparticle-based platform for efficient gene knockdown of targeted cells in the circulation
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DOI：
10.1038/gt.2009.76
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发表时间：
2009-10-01
期刊：
影响因子：
5.1
通讯作者：
King, M. R.
中科院分区：
文献类型：
--
作者：
Huang, Z.;King, M. R.
已经确定，内皮细胞的粘附分子与白细胞上的受体之间的特异性相互作用可以将白细胞从血流中分离并募集到炎症和凝血部位。以前，我们表明，P-选择素可以被吸收到血液相容性microrenathane管的表面上，并且P-选择素涂覆的表面可以成功地从体外生理剪切流和体内血流中捕获P-选择素受体阳性干细胞。本文将P-选择素共价结合到纳米脂质体表面，制备靶向纳米粒。小干扰RNA（siRNA）被这些纳米级脂质体包封，并且脂质体通过用DSPE-PEG 2000进行PEG化来稳定。实验表明，这些P-选择素-、聚乙二醇化-、纳米级-脂质体（PS-DSPE-PEG NPs）可以吸附到微血管内表面。包被的表面可以从生理剪切流中特异性捕获靶细胞，有效地将包裹的siRNA递送到粘附细胞中，并显着沉默靶基因中性粒细胞弹性蛋白酶。通过该设备，我们在循环系统中产生了高局部浓度的siRNA递送，为循环靶细胞提供了足够的时间与治疗材料相互作用。SiRNA被有效地递送到特定的靶细胞中，从而为高效siRNA转染和循环中的其他治疗材料递送提供了有力的工具。该方法应证明对源自血细胞紊乱的疾病特别有用。Gene Therapy（2009）16，1271-1282; doi：10.1038/gt.2009.76; 2009年6月25日在线发表
It is well established that specific interaction between adhesion molecules of endothelial cells and receptors on leukocytes can separate and recruit leukocytes from the bloodstream to sites of inflammation and coagulation. Previously, we showed that P-selectin can be absorbed onto the surface of a blood-compatible microrenathane tube, and the P-selectin-coated surface could successfully capture P-selectin receptor-positive stem cells from physiological shear flow in vitro and from the bloodstream in vivo. In this paper, P-selectin was covalently attached to the surface of nanoscale liposomes to create targeting nanoparticles (NPs). Small interfering RNA (siRNA) was encapsulated by these nanoscale liposomes, and the liposomes were stabilized by PEGylation with DSPE-PEG2000. Experiments showed that these P-selectin-, PEGylated-, nanoscale-liposomes (PS-DSPE-PEG NPs) could be absorbed onto the inner surface of microrenathane tubing. The coated surface could specifically capture targeted cells from physiological shear flow, efficiently deliver encapsulated siRNA into adherent cells and dramatically silence the targeted gene neutrophil elastase. With this device, we create a high localized concentration for siRNA delivery in the circulatory system, providing circulating target cells adequate time to interact with therapeutic materials. SiRNA is efficaciously delivered into specific target cells, thereby providing a powerful tool for highly efficient siRNA transfection and other therapeutic materials delivery in circulation. The method should prove especially useful for diseases derived from disorders of blood cells. Gene Therapy (2009) 16, 1271-1282; doi: 10.1038/gt.2009.76; published online 25 June 2009