Engineering oxygen vacancy of MoOx nanoenzyme by Mn doping for dual-route cascaded catalysis mediated high tumor eradication

There is an urgent need to develop photosensitive nanoenzymes with better phototherapeutic efficiency through simple processes. By exploiting semiconductor catalysis and defect chemistry principles, herein, a MnMoOx composite semiconductor nanoenzyme was developed to achieve a fully integrated theranostic nanoenzyme for highly efficient photo/chemo-enzyme-dynamic eradication of deep tumors. Relative to iron oxides, manganese oxides offer ideal catalytic performance under near-neutral conditions, which helps to broaden the suitable pH range of the MnMoOx nanoenzyme for antitumor therapy. Furthermore, with the assistance of glutathione depletion, Mn4+/Mo6+ was successfully converted to Mn2+/Mo5+, inhibiting the scavenging of reactive oxygen species (ROS) and promoting cycling. Therefore, MnMoOx has favorable catalase (CAT)-like activity and oxidase (OXD)-like activity in the tumor microenvironment (TME) for promoting the "H2O2O2O2-" and "H2O2OH" cascade reactions. The abundant oxygen vacancy defects also promote the surface plasmon resonance (SPR) effect in the second near-infrared (NIR-II) window of MnMoOx, which significantly enhanced its photothermal therapy (PTT) effect and catalytic activity. In detail, ROS production was significantly enhanced due to the adsorption of water and oxygen molecules by the rich oxygen vacancies of MnMoOx. MnMoOx also exhibited excellent multi-modal imaging activity (including computed tomography (CT), magnetic resonance imaging (MRI), and photoacoustic (PA)), which can be exploited to better guide the administration of medication.