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Green formulation and chemical characterization of Lens culinaris seed aqueous extract conjugated gold nanoparticles for the treatment of acute myeloid leukemia in comparison to mitoxantrone in a leukemic mouse model
Authors:Ahmad Ahmeda  Mohammad Mahdi Zangeneh  Akram Zangeneh
Institution:1. Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar;2. Department of Clinical Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran
Abstract:The high prevalence of cancer has been increased the rate of studying about the new formulation of chemotherapeutic drugs. In this regards, one of the suitable options is the use of metal nanoparticles for formulating these drugs. In the recent study, Lens culinaris seed aqueous extract conjugated gold nanoparticles (AuNPs) are reported for the first time to exert a dietary therapeutic potential compared to mitoxantrone in an animal model of acute myeloid leukemia. The synthesized AuNPs were characterized using different techniques including UV–Vis., FT-IR, XRD, FE-SEM, and TEM. DPPH free radical scavenging test was done to evaluate the antioxidant potentials of HAuCl4, L. culinaris, AuNPs, and mitoxantrone. For the analyzing of cytotoxicity effects of HAuCl4, L. culinaris, AuNPs, and mitoxantrone, MTT assay was used on HUVEC, 32D-FLT3-ITD, Human HL-60/vcr, and Murine C1498 cell lines. In vivo assay, induction of acute myeloid leukemia was done by 7,12-Dimethylbenza]anthracene (DMBA) in 75 mice. Then, the animals were randomly divided into six subgroups, including control, untreated, HAuCl4, L. culinaris, AuNPs, and mitoxantrone. SEM and TEM images showed uniform spherical morphology and average diameters of 10–40 nm for the nanoparticles. DPPH test revealed similar antioxidant potentials for mitoxantrone and AuNPs. Similar to mitoxantrone, AuNPs had low cell viability dose-dependently against 32D-FLT3-ITD, Human HL-60/vcr, and Murine C1498 cell lines without any cytotoxicity on HUVEC cell line. AuNPs and mitoxantrone significantly (p ≤ 0.05) reduced the weight and volume of liver and spleen, the pro-inflammatory cytokines, and the total WBC, blast, neutrophil, monocyte, eosinophil, and basophil counts and increased the mRNA expression of Sphingosine-1-phosphate receptor-1 and Sphingosine-1-phosphate receptor-5, the anti-inflammatory cytokines, and the lymphocyte, platelet, and RBC parameters as compared to the untreated mice. It looks that AuNPs can be administrated as a chemotherapeutic supplement or drug for the treatment of acute myeloid leukemia in the clinical trial.
Keywords:acute myeloid leukemia  gold nanoparticles  Lens culinaris  mitoxantrone  seed
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