Gold‑manganese oxide nanocomposite suppresses hypoxia and augments pro-inflammatory cytokines in tumor associated macrophages

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.