Nanozyme‐based Clusterphene for Enhanced Electrically Catalytic Cancer Therapy

Nanozyme mediated catalytic therapy is an attractive strategy for cancer therapy. However, the nanozymes are tended to assemble into 3D architectures, resulting in poor catalytic efficiency for therapy. This study designs the assembly of nanozymes and natural enzymes into the layered structures featuring hexagonal pores as nanozyme clusterphene and investigates their catalytic therapy with the assistance of electric field. The nanozyme-based clusterphene consists of polyoxometalate (POM) and natural glucose oxidase (GOx), named POMG-based clusterphene, which facilitate multi-enzyme activities including peroxidase (POD), catalase (CAT), and glutathione oxidase (GPx). The highly ordered layers with hexagonal pores of POMG units significantly improve the peroxidase-like (POD-like) activity of the nanozyme and thus the sustained production of reactive oxygen species (ROS). At the same time, GOx can increase endogenous H2O2 and produce gluconic acid while consuming glucose, the nutrient of tumor cell growth. The results indicate that the POD-like activity of POMG-based clusterphene increase approximately sevenfold under electrical stimulation compared with Nd-substituted keggin type POM cluster (NdPW11). The experiments both in vitro and in vivo show that the proposed POMG-based clusterphene mediated cascade catalytic therapy is capable of efficient tumor inhibiting and preventing tumor proliferation in tumor-bearing mice model, promising as an excellent candidate for catalytic therapy.