HIF1A and neoplasm: Since multicellular tumor spheroids (MTCS) could accurately replicate the heterogeneity of tumor microenvironment with a hypoxic core and normoxic surface42,43, we then embarked on constructing 4T1 MCTS to investigate the effect of MnO2@PtCo nanoflowers on mitigating hypoxia by employing hypoxia inducible factor (HIF)-1α staining assay.