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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

Zaimy, M.A. and Jebali, A. and Bazrafshan, B. and Mehrtashfar, S. and Shabani, S. and Tavakoli, A. and Hekmatimoghaddam, S.H. and Sarli, A. and Azizi, H. and Izadi, P. and Kazemi, B. and Shojaei, A. and Abdalaian, A. and Tavakkoly-Bazzaz, J. (2016) 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, 23 (9). pp. 315-320.

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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 HAuCl 4 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. © 2016 Nature America, Inc., part of Springer Nature.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: 3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide; antisense oligonucleotide; aptamer; ascorbic acid; BAG 1 protein; CD33 antigen; CD34 antigen; doxorubicin; gold nanoparticle; heparin; inhibitor of apoptosis protein; protein bcl 2; protein MDM2; RNA; survivin, acute myeloblastic leukemia; acute myeloid leukemia subtype M2; antisense therapy; Article; atomic force microscopy; blood sampling; cancer gene therapy; cancer inhibition; cell death; cell isolation; cell viability; clinical article; controlled study; dose response; down regulation; drug synthesis; evaluation study; gene overexpression; gene silencing; heparinization; human; human cell; MTT assay; nonviral gene therapy; oncogene; priority journal; real time polymerase chain reaction; RNA structure; scanning electron microscopy
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: UNSPECIFIED
Depositing User: GOUMS
Date Deposited: 13 Jun 2017 05:15
Last Modified: 13 Jun 2017 05:15
URI: http://eprints.goums.ac.ir/id/eprint/4915

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