title: Coinhibition of overexpressed genes in acute myeloid leukemia subtype M2 by gold nanoparticles functionalized with five antisense oligonucleotides and one anti-CD33(+)/CD34(+) aptamer.
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.
authors: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: M A
authors: MA
authors: Zaimy
authors: Advanced Medical Sciences and Technologies Department, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors: A
authors: A
authors: Jebali
authors: Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
authors: B
authors: B
authors: Bazrafshan
authors: Department of Biology, Faculty of Basic Sciences, University of Guilan, Rasht, Iran.
authors: S
authors: S
authors: Mehrtashfar
authors: Department of Biology, Faculty of Science, Zabol University, Zabol, Iran.
authors: S
authors: S
authors: Shabani
authors: Department of Molecular Genetics, Science and Research Branch, Islamic Azad University, Zanjan, Iran.
authors: A
authors: A
authors: Tavakoli
authors: Advanced Medical Sciences and Technologies Department, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors: S H
authors: SH
authors: Hekmatimoghaddam
authors: Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors: A
authors: A
authors: Sarli
authors: Department of Medical Parasitology, Zabol University of Medical Sciences, Zabol, Iran.
authors: H
authors: H
authors: Azizi
authors: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: P
authors: P
authors: Izadi
authors: Department of Biotechnology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: B
authors: B
authors: Kazemi
authors: Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors: A
authors: A
authors: Shojaei
authors: Department of Chemical Engineering, Princeton University, Princeton, NJ, USA.
authors: A
authors: A
authors: Abdalaian
authors: Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: J
authors: J
authors: Tavakkoly-Bazzaz
mesh_terms: D018952:Antigens, CD34 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D015870:Gene Expression; D006046:Gold; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics*; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000235:genetics*
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D014408:Biomarkers, Tumor; C571163:CD33 protein, human; D016376:Oligonucleotides, Antisense; D063268:Sialic Acid Binding Ig-like Lectin 3; D006046:Gold