CoNiCoNC tumor therapy by two-ways producing HO to aggravate energy metabolism, chemokinetics, and ferroptosis.

The effectiveness of chemokinetic therapy nanozymes is severely constrained because of the low HO levels in the tumor microenvironment. Unlike other self-produced HO nanozymes, the N-CNTs-encapsulated CoNi alloy (CoNiCoNC) with glucose oxidase and lactate oxidase activities has two ways to produce HO. It can facilitate the transformation of glucose and lactic acid into HO simultaneously. First, the HO generation pathway is favorable for aggravating energy metabolism. Second, some produced HO can be decomposed by CoNiCoNC to HO and O with the 4e pathway to alleviate the TME hypoxia. Third, HO can be catalyzed to form OH to enhance reactive oxygen species (ROS) content. Through proteomic analysis, nanozymes substantially impact the metabolic pathways of cancer cells because of their aggravating energy metabolism. The high levels of ROS can cause mitochondrial lipid peroxidation and cellular ferroptosis. Consequently, the two-way HO-selective nanoenzymatic platform realizes the synergistic effect of starvation therapy and chemokinetics.