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PinX1小干扰RNA/甲氧基聚乙二醇-聚乙烯亚胺-超顺磁性氧化铁纳米粒子联合阿霉素增强对胶质瘤生长的抑制作用。

PinX1-siRNA/mPEG-PEI-SPION combined with doxorubicin enhances the inhibition of glioma growth.

作者信息

Long Ling, Wang Weiwei, Cai Xia-Dong, Cheng DU, Shuai Xintao, Peng Ying

机构信息

Department of Neurology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China ; Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, P.R. China.

Center of Biomedical Engineering, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, Guangdong 510275, P.R. China.

出版信息

Exp Ther Med. 2014 May;7(5):1170-1176. doi: 10.3892/etm.2014.1586. Epub 2014 Feb 26.

DOI:10.3892/etm.2014.1586
PMID:24940406
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3991531/
Abstract

Resistance to chemotherapy and the side effects of anticancer drugs are the major obstacles for glioma treatment. The aim of the present study was to develop a novel approach for the treatment of gliomas that improved the therapeutic effect; the anticancer drug, doxorubicin (DOX), was combined with short interfering (si)RNA and monomethoxy polyethylene glycol polyethylenimine superparamagnetic iron oxide nanoparticle (mPEG-PEI-SPION), a magnetic resonance imaging (MRI)-visible nanoparticle. Specific siRNA molecules, delivered by mPEG-PEI-SPION, were employed to knockdown the PIN2-interacting protein 1 (PinX1) gene in C6 glioma cells. PinX1 is a nucleolar protein associated with telomere and telomerase. C6 cells were treated with DOX and/or PinX1-siRNA. The results of the transfection experiments revealed that siRNA/mPEG-PEI-SPION was transfected into C6 cells with high efficiency. PinX1-siRNA was unable to inhibit C6 cells, while in the PinX1-siRNA + DOX group, the same dose of DOX caused an increased loss of cell viability. Therefore, mPEG-PEI-SPION was shown to be viable for siRNA delivery into C6 cells and coadministration of DOX with PinX1-siRNA may be a potential therapeutic method for inhibiting gliomas.

摘要

对化疗的耐药性和抗癌药物的副作用是胶质瘤治疗的主要障碍。本研究的目的是开发一种新的胶质瘤治疗方法以提高治疗效果；将抗癌药物阿霉素（DOX）与短干扰（si）RNA和单甲氧基聚乙二醇聚乙烯亚胺超顺磁性氧化铁纳米颗粒（mPEG-PEI-SPION，一种磁共振成像（MRI）可见的纳米颗粒）相结合。由mPEG-PEI-SPION递送的特异性siRNA分子用于敲低C6胶质瘤细胞中的PIN2相互作用蛋白1（PinX1）基因。PinX1是一种与端粒和端粒酶相关的核仁蛋白。用DOX和/或PinX1-siRNA处理C6细胞。转染实验结果显示，siRNA/mPEG-PEI-SPION能高效转染进入C6细胞。PinX1-siRNA无法抑制C6细胞，而在PinX1-siRNA + DOX组中，相同剂量的DOX导致细胞活力丧失增加。因此，mPEG-PEI-SPION被证明可用于将siRNA递送至C6细胞，并且DOX与PinX1-siRNA联合给药可能是一种抑制胶质瘤的潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/607b692818ff/ETM-07-05-1170-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/dd83a5ec7a83/ETM-07-05-1170-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/c73b827f6c59/ETM-07-05-1170-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/7faec87dbf66/ETM-07-05-1170-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/dfc68900194e/ETM-07-05-1170-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/607b692818ff/ETM-07-05-1170-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/dd83a5ec7a83/ETM-07-05-1170-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/c73b827f6c59/ETM-07-05-1170-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/7faec87dbf66/ETM-07-05-1170-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/dfc68900194e/ETM-07-05-1170-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5d7/3991531/607b692818ff/ETM-07-05-1170-g04.jpg

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