Multifaceted Elevation of ROS Generation for Effective Cancer Suppression

The in situ lactate oxidase (LOx) catalysis is highly efficient in reducing oxygen to H(2)O(2) due to the abundant lactate substrate in the hypoxia tumor microenvironment. Dynamic therapy, including chemodynamic therapy (CDT), photodynamic therapy (PDT), and enzyme dynamic therapy (EDT), could generate reactive oxygen species (ROS) including ·OH and (1)O(2) through the disproportionate or cascade biocatalytic reaction of H(2)O(2) in the tumor region. Here, we demonstrate a ROS-based tumor therapy by integrating LOx and the antiglycolytic drug Mito-LND into Fe(3)O(4)/g-C(3)N(4) nanoparticles coated with CaCO(3) (denoted as FGLMC). The LOx can catalyze endogenous lactate to produce H(2)O(2), which decomposes cascades into ·OH and (1)O(2) through Fenton reaction-induced CDT and photo-triggered PDT. Meanwhile, the released Mito-LND contributes to metabolic therapy by cutting off the source of lactate and increasing ROS generation in mitochondria for further improvement in CDT and PDT. The results showed that the FGLMC nanoplatform can multifacetedly elevate ROS generation and cause fatal damage to cancer cells, leading to effective cancer suppression. This multidirectional ROS regulation strategy has therapeutic potential for different types of tumors.