Green synthesis and chemical characterization of Thymus vulgaris leaf aqueous extract conjugated gold nanoparticles for the treatment of acute myeloid leukemia in comparison to doxorubicin in a leukemic mouse model

Abstract

Recently, metallic nanoparticles have been used for the treatment of several disorders, such as cancer. Indeed, finding the chemotherapeutic drug of nanoparticles is in researching the priority of both developed and developing countries. The present study confirms the ability of aqueous extract of Thymus vulgaris grown under in vitro condition for the biosynthesis of gold nanoparticles (AuNPs). Also, in this study, we indicated the antioxidant, cytotoxicity, and anti‐acute myeloid leukemia properties of AuNPs compared to doxorubicin in a leukemic mouse model. The synthesized AuNPs were characterized using different techniques including X‐ray diffraction (XRD), energy Dispersive X‐ray Spectrometry (EDS), fourier‐transform infrared spectroscopy (FT‐IR) spectroscopy, ultraviolet–visible spectroscopy (UV–Vis.), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In vivo design, induction of acute myeloid leukemia was done by 7,12‐Dimethylbenz[a]anthracene (DMBA) in 75 mice. Then, the animals were randomly divided into six subgroups, including control, untreated, doxorubicin, AuNPs, T. vulgaris, and HAuCl4. By quantitative real‐time PCR, sphingosine‐1‐phosphate receptor‐1 and sphingosine‐1‐phosphate receptor‐5 mRNA expression in lymphocytes were significantly (P ≤ 0.01) raised by treating the leukemic mice with the AuNPs and doxorubicin. Also, AuNPs similar to doxorubicin, significantly (P ≤ 0.01) enhanced the anti‐inflammatory cytokines (IL4, IL5, IL10, IL13, and IFNα) and the platelet, lymphocyte, and red blood cell (RBC) parameters and reduced the pro‐inflammatory cytokines (IL1, IL6, IL12, IL18, IFNY, and TNFα), and the total white blood cell (WBC), blast, monocyte, neutrophil, eosinophil, and basophil counts as compared to the untreated mice. In vitro design, 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) test revealed similar antioxidant potentials for doxorubicin and AuNPs. Furthermore, AuNPs similar to doxorubicin 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. Above results confirm the excellent antioxidant, cytotoxicity, and anti‐acute myeloid leukemia effects of AuNPs compared to doxorubicin. After confirming these results in clinical trial studies, AuNPs can be used as a chemotherapeutic drug for the treatment of acute myeloid leukemia in human.