NIR-photocatalytic LDHB-mimetic CuS@ZnS nanoenzyme regulates arthritis microenvironment through lactate oxidation and hydrogen evolution

Lactate (LA) undergoes abnormal metabolism in the microenvironment of rheumatoid arthritis (RA), and its excessive accumulation activates a cascade of intracellular signals, acting as an inflammatory enhancer. Clearing LA while simultaneously regulating the polarization of macrophage cells can improve long-term therapeutic outcomes. Here, we developed photocatalytic biomimetic nano enzymes to address multiple factors in RA by generating hydrogen to control innate immunity and reducing LA to restore the immune system. Heterostructured nanocrystals using plasmonic copper and zinc monosulfide could be explored for anomalous plasmon-induced electron transfer for NIR-induced photocatalytic activity in the hydrogen evolution reaction. In our study, overexpressed LA as a sacrificial agent for NIR photocatalytic therapy is depleted; generated hydrogen could scavenge intracellular reactive oxygen species, regulate polarization of M1 to M2 macrophages that could inhibit cytokine storms, thus alleviating inflammation of collagen induced mouse model. This "two-for-one" photocatalytic biomimetic nanoenzyme strategy of oxidative consumption of LA and targeted delivery of hydrogen opens up a potential strategy for treating progressive arthritis.