ABSTRACT
The tumor microenvironment, essentially hypoxic, is sustained by the hypoxia inducing factor (HIF), released from the pro-tumorigenic tumor associated macrophages (TAMs), functionally identical to the M2 phenotype macrophages. Stability of HIF mainly depends on molecular oxygen and an iron-dependent enzyme prolyl hydroxylase, while its activity may be inhibited by high levels of reactive oxygen species and nitric oxide. The present work showcases a novel approach utilizing the anti-tumorigenic potential of a gold-manganese oxide nanocomposite material in the tumor microenvironment that affects tumor hypoxia, exploring the possibility of restoring the immunoregulatory nature of TAMs from their pro-tumorigenic state. Along with the biochemical markers, ELISA and FACS analyses have also confirmed the potential of these nanoparticles in reverting back the M2 phenotype of TAMs to their classically activated M1 phenotype.
Subject(s)
Fibrosarcoma/therapy , Gold/therapeutic use , Hypoxia/therapy , Macrophages/physiology , Manganese Compounds/therapeutic use , Oxides/therapeutic use , Animals , Cell Differentiation/drug effects , Cells, Cultured , Cytokines/metabolism , Fibrosarcoma/immunology , Gold/chemistry , Hypoxia/immunology , Inflammation Mediators/metabolism , Iron/metabolism , Male , Manganese Compounds/chemistry , Mice , Nanocomposites/chemistry , Nitric Oxide/metabolism , Oxidation-Reduction , Oxides/chemistry , Prolyl Hydroxylases/metabolism , Th1 Cells/immunology , Th2 Cells/immunology , Tumor MicroenvironmentABSTRACT
Para-aminobenzoic acid (PABA) stabilised zinc oxide (ZnO) quantum dots (QDs) have been synthesised by refluxing zinc acetate dihydrate in methanol under alkaline condition and re-dispersed into water by centrifugation. Aqueous dispersion of PABA-stabilised ZnO QDs was taken with seven different organic solvents in test tubes and subjected to diazo reaction under specified conditions. It was seen that the quantum dots assembled into diverse superstructures depending on the nature of the immiscible solvent at the aqueous-organic interface. The assemblies so obtained have been characterised by energy dispersive X-ray (EDX) analysis, Fourier transform infrared (FTIR), fluorescence and Raman spectroscopy, X-ray diffraction (XRD) and thermogravimetric analysis (TGA), optical, fluorescence and scanning electron microscopic (SEM) images. It has been observed that the ensuing supramolecular assemblies exhibit significant electrical conductivity and photoluminescence properties.
