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首页> 外文期刊>Biochimie >Aptameric GT oligomers need to be complexed to ethoxylated polyethylenimine as pre-paired duplexes to efficiently exert their cytotoxic activity in human lymphoblastic cancer cells
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Aptameric GT oligomers need to be complexed to ethoxylated polyethylenimine as pre-paired duplexes to efficiently exert their cytotoxic activity in human lymphoblastic cancer cells

机译：Aptameric GT寡聚体需要与乙氧基化的聚乙烯亚胺复合成预配对双链体，以有效发挥其在人淋巴母细胞癌细胞中的细胞毒活性

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摘要

The aptameric oligonucleotides GT were found to exert a selective, specific and dose-dependent cell growth inhibition effect on a variety of human cancer cells by recognising specific nuclear proteins and among these in particular an isoform of the eukaryotic elongation factor 1A1 (EEF1 A1). The potential development of these aptameric oligomers needs that they retain serum and intracellular stabilities. Polycations are safe non-viral carriers of the nucleic acids. We demonstrated that a weakly basic polycation, the ethoxylated polyethylenimine (EPEI), can efficiently deliver cytotoxic GT oligomers when they were complexed as partial pre-paired duplex. In this way, nuclease-resistance of the oligomer was markedly improved and the administration of the duplex complexed with EPEI to lymphoblastic cancer cells caused a specific cytotoxic effect at concentrations lower than that of naked GT. However, the cytotoxic activity of the oligomer-EPEI complex resulted strictly related to the GC content and Tm of the duplex region. The single-stranded GT and the duplex with high GC content and Tm, although complexed with EPEI failed to exert cytotoxicity. Overall results indicated that aptameric oligomers complexed with polycations can be efficiently delivered into the cells and display the desired biological effect designing a balanced partial duplex whose stability can allow oligomer release from the polycation under the physiological cellular conditions.
机译：发现适体寡核苷酸GT通过识别特异性核蛋白，尤其是其中的真核伸长因子1A1（EEF1 A1）的同种型，对多种人类癌细胞产生选择性，特异性和剂量依赖性的细胞生长抑制作用。这些适体寡聚物的潜在发展需要它们保留血清和细胞内稳定性。聚阳离子是核酸的安全的非病毒载体。我们证明了弱碱性聚阳离子，乙氧基化聚乙烯亚胺（EPEI），当它们被复合为部分预配对的双链体时，可以有效地递送细胞毒性的GT低聚物。以此方式，寡聚物的核酸酶抗性得到显着改善，并且将与EPEI复合的双链体给予淋巴母细胞癌细胞以低于裸GT的浓度引起特异性细胞毒性作用。然而，导致的低聚物-EPEI复合物的细胞毒活性与双链体区域的GC含量和Tm严格相关。单链GT和具有高GC含量和Tm的双链体，尽管与EPEI复合，但未发挥细胞毒性作用。总体结果表明，与聚阳离子复合的适体低聚物可以有效地传递到细胞中，并显示出所需的生物学效应，从而设计出平衡的部分双链体，其稳定性可以使低聚物在生理细胞条件下从聚阳离子中释放出来。

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