Synthesis and application of Au NPs-chitosan nanocomposite in the treatment of acute myeloid leukemia in vitro and in vivo

In recent days, novel biomolecule stabilized nanocomposites have come into prominence as featured next generation materials. In this article we have green synthesized Au nanoparticles being deposited and stabilized over chitosan (CS) molecules. The electron rich polar functional groups of chitosan have been exploited to cap the Au NPs. The structural and physical features of Au NPs-CS nanocomposite was analyzed with different techniques like Ultraviolet–Visible Spectroscopy, Fourier Transform Infrared Spectroscopy, Field Emission Scanning Electron Microscope, Transmission Electron Microscopy, and Energy-Dispersive X-Ray Spectroscopy techniques. Recently, noble metal nanoparticles have been used in the treatment of different cancers. This has prompted us to use our nanocomposite in the treatment of acute myeloid leukemia (AML) both in vitro and in vivo. Initially, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was performed to study the excellent antioxidant properties of Au NPs-CS nanocomposite. For in vitro cytotoxicity studies, HUVEC normal cell line, 32D-FLT3-ITD and Murine C1498 cancer cell lines were used and the nanocomposite was found of comparable potential as the standard AML drug Daunorubicin. For in vivo studies, 7,12-Dimethylbenz[a]anthracene (DMBA) was injected for inducing AML over 50 mice and then the drug as well as the nanocomposite was administered. Subsequently, comparison of different immunological, hematological, biochemical, stereological parameters and S1PR1 and S1PR5 mRNA expressions were ascertained. By quantitative real-time polymerase chain reaction, S1PR1 and S1PR5 mRNA expression in lymphocytes were significantly (p ≤ 0.05) raised by treating the leukemic mice with the nanocomposite. Also, nanocomposite significantly (p ≤ 0.05) decreased the weight and volume of liver and spleen, the pro-inflammatory cytokines, and the total white blood cells, blast, neutrophil, monocyte, eosinophil, and basophil counts, increased the anti-inflammatory cytokines and the lymphocyte, platelet and red blood cells parameters, and regulated the biochemical parameters as compared to the untreated mice. An extensive study was done on these biological experiments using the Au NPs-CS nanocomposite and we achieved fascinating results such that it could be used as an alternative prospective chemotherapeutic drug for the treatment of acute myeloid leukemia.