Preparation and synthesis a new chemotherapeutic drug of silver nanoparticle-chitosan composite; Chemical characterization and analysis of their antioxidant,cytotoxicity, and anti-acute myeloid leukemia effects in comparison to Daunorubicin in a leukemic mouse model

Nanoparticles usually have better outcomes than the bulk samples of the same element because they possess a higher specificity level than the larger particles. This is also true for silver nanoparticles, and little amount of these materials has high remedial effects. Silver nanoparticles are used as a therapeutic tool for the treatment of several diseases such as cancer. In this study, silver nanoparticles using chitosan (AgNPs-chitosan composite) are reported for the first time to exert a dietary therapeutic potential compared to Daunorubicin in an animal model of acute myeloid leukemia. The synthesized AgNPs-chitosan composite was characterized using different techniques including ultraviolet–visible spectroscopy, fourier-transform infrared spectroscopy, energy dispersive X-ray spectrometry, scanning electron microscopy, and transmission electron microscopy. FTIR findings suggested antioxidant compounds in the nanoparticles were the sources of reducing power, reducing silver ions to AgNPs. SEM and TEM images exhibited a uniform spherical morphology and average diameters of 30 nm for the nanoparticles. Then, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging test was done to evaluate the antioxidant potentials of Daunorubicin, AgNO₃, chitosan, and AgNPs-chitosan composite. DPPH test revealed similar antioxidant potentials for Daunorubicin and AgNPs-chitosan composite. For the analyzing of cytotoxicity effects of Daunorubicin, AgNO₃, chitosan, and AgNPs, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidefor (MTT) assay was used on HUVEC, 32D-FLT3-ITD, and Murine C1498 cell lines. AgNPs-chitosan composite similar to Daunorubicin had low cell viability dose-dependently against 32D-FLT3-ITD and Murine C1498 cell lines without any cytotoxicity on HUVEC cell line. In vivo design, induction of acute myeloid leukemia was done by 7,12-Dimethylbenz[a]anthracene in 50 mice. Then, the animals were randomly divided into six subgroups, including control, untreated, Daunorubicin, AgNO₃, chitosan, and AgNPs-chitosan composite. Similar to Daunorubicin, AgNPs-chitosan composite significantly (P ≤ .01) decreased the weight of the body, the pro-inflammatory cytokines, and the total white blood cells, blast, neutrophil, monocyte, eosinophil, and basophil counts and increased the anti-inflammatory cytokines and the lymphocyte, platelet, and red blood cell parameters as compared to the untreated mice. These results show that the inclusion of chitosan improves the therapeutic properties of AgNPs-chitosan composite, which led to a significant enhancement in the antioxidant, cytotoxicity, and anti-acute myeloid leukemia activities of the nanoparticles. It appears that AgNPs-chitosan composite can be used as a chemotherapeutic drug for the treatment of acute myeloid leukemia in the clinical trial.