Green synthesis and formulation a modern chemotherapeutic drug of Spinacia oleracea L. leaf aqueous extract conjugated silver nanoparticles; Chemical characterization and analysis of their cytotoxicity, antioxidant, and anti‐acute myeloid leukemia properties in comparison to doxorubicin in a leukemic mouse model

Abstract

There is an increasing commercial demand for nanoparticles due to their wide applicability in various areas such as electronics, catalysis, chemistry, energy, and medicine. Recently, researchers have tried to synthesize the chemotherapeutic drugs from metallic nanoparticles especially gold and silver nanoparticles. In the current study, silver nanoparticles using Spinacia oleracea L. leaf aqueous extract (AgNPs) are reported for the first time to exert a dietary remedial property compared to doxorubicin in an animal model of acute myeloid leukemia. The synthesized AgNPs were characterized using different techniques including UV‐Vis., EDS, TEM, FT‐IR, and FE‐SEM. UV‐Vis. indicates an absorption band at 462 nm that is related to the surface plasmon resonance of AgNPs. In EDS, metallic silver nanocrystals indicated an optical absorption peak at roughly 4keV. TEM and FE‐SEM images exhibited a uniform spherical morphology and diameters of 20–40 nm for the nanoparticles. FT‐IR findings suggested antioxidant compounds in the nanoparticles were the sources of reducing power, reducing silver ions to AgNPs. In vivo design, induction of acute myeloid leukemia was done by 7,12‐Dimethylbenz[a]anthracene in 75 mice. Then, the animals were randomly divided into six subgroups, including control, untreated, AgNO3, S. oleracea, AgNPs, and doxorubicin. Similar to doxorubicin, AgNPs significantly (p ≤ 0.01) reduced the pro‐inflammatory cytokines, and the total WBC, blast, neutrophil, monocyte, eosinophil, and basophil counts and increased the weight of the body, the anti‐inflammatory cytokines and the lymphocyte, platelet, and RBC parameters as compared to the untreated mice. DPPH free radical scavenging test was done to evaluate the antioxidant potentials of AgNO3, S. oleracea, AgNPs, and doxorubicin. DPPH test revealed similar antioxidant potentials for doxorubicin and AgNPs. For the analyzing of cytotoxicity effects of AgNO3, S. oleracea, AgNPs, and doxorubicin, MTT assay was used on HUVEC, Human HL‐60/vcr, 32D‐FLT3‐ITD, and Murine C1498 cell lines. AgNPs similar to doxorubicin had low cell viability dose‐dependently against Human HL‐60/vcr, 32D‐FLT3‐ITD, and Murine C1498 cell lines without any cytotoxicity on HUVEC cell line. These results reveal that the inclusion of S. oleracea leaf aqueous extract improves the remedial effects of AgNPs, which led to a significant enhancement in the antioxidant, cytotoxicity, and anti‐acute myeloid leukemia potentials of the nanoparticles. It seems that AgNPs can be applied as a chemotherapeutic supplement or drug for the treatment of acute myeloid leukemia in the clinical trial.