Delivery Efficiency of miR-21i-CPP-SWCNT and Its Inhibitory Effect on Fibrosis of the Renal Mesangial Cells

Delivery Efficiency of miR-21i-CPP-SWCNT and Its Inhibitory Effect on Fibrosis of the Renal Mesangial Cells
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miR-21i-CPP-SWCNT的递送效率及其对肾系膜细胞纤维化的抑制作用

DOI:
10.1155/2016/3451685
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发表时间:
2016-11
期刊:
Journal of Nanomaterials.
影响因子:
--
通讯作者:
Xiaozhong Qiu
Xiaozhong Qiu
中科院分区:
其他
文献类型:
--
作者:
Hong Liu;Guobao Wang;Yihong Yang;Lei Yu;Leyu Wang;Zhengda Wen;Xiaofang Hu;Hequn Zou;Xiaozhong Qiu

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MicroRNA 21 miR-21被证实可引起肾纤维化,抑制miR-21可改善肾细胞癌疾病的不良预后。成熟miR-21的互补寡核苷酸被认为是一种有效的细胞内miR-21抑制剂miR-21i。将miR-21i直接有效递送到纤维化细胞中是治疗肾纤维化的一种简便方法。本文将通过单壁碳纳米管SWCNT和细胞穿透肽CPP合成的miR-21i-CPP-SWCNT递送系统作为一种新的纤维化靶向治疗载体。miR-21i和CPP首先通过静电力结合在一起,随后miR-21i-CPP通过疏水力与SWCNTs表面结合。CPP可以使递送系统具有靶向性,而swcnts可以增强其穿透能力。从设计的miR-21i- cpp - swcnts中释放的外源性miR-21i成功地抑制了肾系膜细胞RMCs中纤维化相关蛋白的表达。我们发现TGF-β1蛋白的表达比α-SMA蛋白的表达对miR-21i-CPP-SWCNT更敏感。
MicroRNA 21 miR-21 was proved to cause renal fibrosis and the inhibition of miR-21 would improve the poor prognosis in renal cell carcinoma diseases. The complementary oligonucleotide of mature miR-21 was considered to be an effective intracellular miR-21 inhibitor miR-21i. The directly effective delivery of miR-21i into fibrotic cell is a facile method for treatment of renal fibrosis. Herein, the miR-21i-CPP-SWCNT delivery system, synthesized via single-walled carbon nanotube SWCNT and cell-penetrating peptide CPP, was taken as a novel fibrosis-targeting therapeutic carrier. The miR-21i and CPP firstly bind together via electrostatic forces, and subsequently miR-21i-CPP binds to the surface of SWCNTs via hydrophobic forces. CPP could endow the delivery system with targeting property, while SWCNT would enhance its penetrating ability. The exogenous miR-21i released from the designed miR-21i-CPP-SWCNTs had successfully inhibited the expression of fibrosis-related proteins in renal mesangial cells RMCs. We found that the expression of TGF-β1 proteins was more sensitive to miR-21i-CPP-SWCNT than the expression of α-SMA proteins.
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