CoNiCoNC tumor therapy by two-ways producing H2O2 to aggravate energy metabolism, chemokinetics, and ferroptosis.

[Display omitted] • CoNiCoNC can catalyze the self-supply of H 2 O 2 from glucose and lactate, alleviating low H 2 O 2 levels in the tumor TME. • CoNiCoNC has the ability to catalyze the production of O2 from H 2 O 2 to alleviate hypoxia in tumor TME. • CoNiCoNC has GSH oxidase-like activity and causes cellular ferroptosis. • CoNiCoNC can catalyze the production of large amounts of ROS by H 2 O 2 in the tumor microenvironment and damage tumor cells. The effectiveness of chemokinetic therapy nanozymes is severely constrained because of the low H 2 O 2 levels in the tumor microenvironment. Unlike other self-produced H 2 O 2 nanozymes, the N -CNTs-encapsulated CoNi alloy (CoNiCoNC) with glucose oxidase and lactate oxidase activities has two ways to produce H 2 O 2. It can facilitate the transformation of glucose and lactic acid into H 2 O 2 simultaneously. First, the H 2 O 2 generation pathway is favorable for aggravating energy metabolism. Second, some produced H 2 O 2 can be decomposed by CoNiCoNC to H 2 O and O 2 with the 4e − pathway to alleviate the TME hypoxia. Third, H 2 O 2 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 H 2 O 2 -selective nanoenzymatic platform realizes the synergistic effect of starvation therapy and chemokinetics. [ABSTRACT FROM AUTHOR]