首页> 外文会议>2015 XVIII AISEM Annual Conference >Polymethylmethacrylate nanoparticles as carrier of an oligodeoxynucleotide molecular beacon specific for survivin mRNA in A549 human lung adenocarcinoma epithelial cells
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Polymethylmethacrylate nanoparticles as carrier of an oligodeoxynucleotide molecular beacon specific for survivin mRNA in A549 human lung adenocarcinoma epithelial cells

机译:聚甲基丙烯酸甲酯纳米颗粒作为A549人肺腺癌上皮细胞中survivin mRNA特异的寡聚脱氧核苷酸分子信标的载体

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In cancer research, the use of antisense oligonucleotide molecular beacons, able to generate a fluorescent signal when they hybridize with their target mRNA, may represent an innovative strategy that conjugates the ability of sensing specific mRNA with the pharmacological silencing activity, preventing the overexpression of proteins associated to cancer development. In cancer context, this approach minimizes the non-specific toxicity and addresses the therapy mainly towards the tumor cells by using effective delivery systems. The aim of this work was to investigate the ability of polymethylmethacrylate nanoparticles (PMMA-NPs) to act as carrier of a theranostic agent, an oligonucleotide molecular beacon (MB) targeting survivin mRNA in A549 human lung adenocarcinoma epithelial cells. Moreover, this paper highlights the need for having an appropriate healthy control in in-vitro experiments. This is a problem widely discussed and felt by the scientific community and often represents a limit recognized in many experimental approaches. In particular, the survivin-MB was firstly characterized in solution in order to verify its functionality and then the PMMA-NPs ability to promote the MB internalization was verified in A549 cells by confocal microscopy. Confluent Human Dermal Fibroblasts from adult (HDFa) were used as healthy control. The results obtained allow us to assess that PMMA-NPs promote the survivin-MB cellular up-take and that the use of 10 μg/mL PMMA-NPs as carrier for survivin-MB for 1h 30 mins might be a promising strategy to reduce cancer cell proliferation avoiding detectable consequences on the healthy cells.
机译:在癌症研究中,使用反义寡核苷酸分子信标(当它们与目标mRNA杂交时能够产生荧光信号)可能代表了一种创新的策略,该策略将感测特定mRNA的能力与药理沉默活性相结合,从而防止了蛋白质的过表达与癌症发展有关。在癌症的背景下,这种方法可最大程度地减少非特异性毒性,并通过使用有效的递送系统主要针对肿瘤细胞进行治疗。这项工作的目的是研究聚甲基丙烯酸甲酯纳米颗粒(PMMA-NPs)作为治疗试剂的载体的能力,治疗试剂是靶向A549人肺腺癌上皮细胞中survivin mRNA的寡核苷酸分子信标(MB)。此外,本文强调了在体外实验中需要适当的健康对照。这是科学界广泛讨论和感觉到的问题,通常代表许多实验方法中公认的局限性。具体而言,首先在溶液中表征survivin-MB以验证其功能性,然后通过共聚焦显微镜在A549细胞中验证PMMA-NPs促进MB内在化的能力。来自成人的融合人皮肤成纤维细胞(HDFa)被用作健康对照。获得的结果使我们能够评估PMMA-NPs促进survivin-MB细胞摄取,并且使用10μg/ mL PMMA-NPs作为survivin-MB的载体持续1h 30分钟可能是减少癌症的一种有前途的策略细胞增殖,避免对健康细胞产生可检测的后果。

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