pH-Responsive Cross-Linked Low Molecular Weight Polyethylenimine as an Efficient Gene Vector for Delivery of Plasmid DNA Encoding Anti-VEGF-shRNA for Tumor Treatment.

pH-Responsive Cross-Linked Low Molecular Weight Polyethylenimine as an Efficient Gene Vector for Delivery of Plasmid DNA Encoding Anti-VEGF-shRNA for Tumor Treatment.
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pH 响应性交联低分子量聚乙烯亚胺作为有效基因载体,用于递送编码抗 VEGF-shRNA 的质粒 DNA,用于肿瘤治疗

DOI:
10.3389/fonc.2018.00354
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发表时间:
2018
影响因子:
4.7
通讯作者:
Yuan WE
Yuan WE
中科院分区:
医学3区
文献类型:
--
作者:
Li X;Guo X;Cheng Y;Zhao X;Fang Z;Luo Y;Xia S;Feng Y;Chen J;Yuan WE

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RNA干扰(RNAi)是一种生物学过程,通过该过程,RNA分子能够以高选择性和特异性抑制基因表达,为肿瘤治疗提供了一种很有前景的手段。通常使用两类分子来使靶基因表达失活:合成的双链小干扰RNA(siRNA)和编码短发夹RNA(shRNA)的质粒DNA。具有高转染效率和低毒性的载体对于siRNA和shRNA的递送至关重要。在本研究中,低分子量聚乙烯亚胺(PEI)的合成衍生物TDAPEI,通过支链PEI(1.8 kDa)与2,5 - 噻吩二甲醛(TDA)的共轭反应,以亚胺键交联。这种可生物降解的阳离子聚合物被用作载体,用于递送表达抗血管内皮生长因子(VEGF)-shRNA的质粒DNA。与PEI(25 kDa)相比,TDAPEI表现更佳,因为实验结果表明,无论是在细胞研究还是动物研究中,它都具有更高的转染效率和更低的毒性。TDAPEI不会激发先天免疫反应,这是基因递送载体设计中应考虑的一个重要因素。所有结果表明,TDAPEI递送抗VEGF - shRNA可能为肿瘤治疗提供一种有前景的方法。
RNA interference (RNAi) is a biological process through which gene expression can be inhibited by RNA molecules with high selectivity and specificity, providing a promising tool for tumor treatment. Two types of molecules are often applied to inactivate target gene expression: synthetic double stranded small interfering RNA (siRNA) and plasmid DNA encoding short hairpin RNA (shRNA). Vectors with high transfection efficiency and low toxicity are essential for the delivery of siRNA and shRNA. In this study, TDAPEI, the synthetic derivative of low-molecular-weight polyethylenimine (PEI), was cross-linked with imine bonds by the conjugation of branched PEI (1.8 kDa) and 2,5-thiophenedicarboxaldehyde (TDA). This biodegradable cationic polymer was utilized as the vector for the delivery of plasmid DNA expressing anti-VEGF-shRNA. Compared to PEI (25 kDa), TDAPEI had a better performance since experimental results suggest its higher transfection efficiency as well as lower toxicity both in cell and animal studies. TDAPEI did not stimulate innate immune response, which is a significant factor that should be considered in vector design for gene delivery. All the results suggested that TDAPEI delivering anti-VEGF-shRNA may provide a promising method for tumor treatment.
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