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Coinhibition of overexpressed genes in acute myeloid leukemia subtype M2 by gold nanoparticles functionalized with five antisense oligonucleotides and one anti-CD33(+)/CD34(+) aptamer

Cancer Gene Therapy volume 23, pages 315–320 (2016)Cite this article

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Abstract

The aim of this study was to evaluate an engineered nanostructure to silence five important oncogenes, including BAG1, MDM2, Bcl-2, BIRC5 (survivin) and XIAP, in acute myeloid leukemia subtype 2 (AML-M2). The smart nanostructures were functionalized gold nanoparticles (FGNs) containing five antisense oligonucleotides (AOs) and one anti-CD33(+)/CD34(+) aptamer. First, the best AO for each gene was selected with the OligoWalk online software, and then different arrangements of AOs were evaluated with the RNAstructure software. Thereafter, naked gold nanoparticles (NGNs) were synthesized by the reaction of 1000 mm HAuCl4 with 10 μg ml−1 ascorbic acid. Next, five AOs and one anti-CD33(+)/CD34(+) aptamer were attached to NGNs through serial reactions. Later, 5 ml of heparinized blood samples from five AML-M2 patients were prepared, cancerous cells were isolated and then incubated with three concentrations (75, 150 and 300 μg ml−1) each of FGNs, NGNs, gold nanoparticles functionalized with scrambled oligonucleotides (GNFSONs) and doxorubicin. Finally, cell death percentage and gene expressions were measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and real-time PCR, respectively. This study showed that FGNs and doxorubicin led to more cell death compared with NGNs and GNFSONs (P<0.05). Interestingly, all concentrations of FGNs led to a decrease in gene expression. As an important finding, although all concentrations of doxorubicin could also inhibit the expression of genes, FGNs had more effect (P<0.05). Moreover, both NGNs and GNFSONs could silence all genes only at a concentration of 300 μg ml−1. For BCL2 and XIAP, a dose-dependent pattern was observed, but there was no similar pattern for others.

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Acknowledgements

This article was extracted from the PhD thesis of Mohammad Ali Zaimy, cosupervised by Dr. J Tavakkoly-Bazzaz and Dr A Jebali. This research was financially supported by the School of Medicine, Tehran University of Medical Sciences, Tehran, Iran (grant number: 31680).

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Author notes

  1. J Tavakkoly-Bazzaz

    Present address: 12Current address: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, 1417614411, Iran. Tel: 09122108444, Fax: 0098-2188953005,

Authors and Affiliations

  1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    M A Zaimy, P Izadi & J Tavakkoly-Bazzaz

  2. Advanced Medical Sciences and Technologies Department, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    A Jebali & S H Hekmatimoghaddam

  3. Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran

    B Bazrafshan

  4. Department of Biology, Faculty of Basic Sciences, University of Guilan, Rasht, Iran

    S Mehrtashfar

  5. Department of Biology, Faculty of Science, Zabol University, Zabol, Iran

    S Shabani

  6. Department of Molecular Genetics, Science and Research Branch, Islamic Azad University, Zanjan, Iran

    A Tavakoli

  7. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    A Sarli

  8. Department of Medical Parasitology, Zabol University of Medical Sciences, Zabol, Iran

    H Azizi

  9. Department of Biotechnology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    B Kazemi

  10. Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

    A Shojaei

  11. Department of Chemical Engineering, Princeton University, Princeton, NJ, USA

    A Abdalaian

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  1. M A Zaimy
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Correspondence to J Tavakkoly-Bazzaz.

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Zaimy, M., Jebali, A., Bazrafshan, B. et al. Coinhibition of overexpressed genes in acute myeloid leukemia subtype M2 by gold nanoparticles functionalized with five antisense oligonucleotides and one anti-CD33(+)/CD34(+) aptamer. Cancer Gene Ther 23, 315–320 (2016). https://doi.org/10.1038/cgt.2016.33

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