Multifunctional nanozyme for tumor-targeted photothermal/catalytic combination therapy†

Catalytic therapy based on nanozymes has emerged as a significant approach to combat tumors. However, catalytic therapy is associated with the big challenge of insufficient treatment. Herein, an N, P dual-doped hollow carbon sphere (HCNPN)-based multifunctional nanozyme (HCNPNs/AGPM) was rationally devised and constructed to achieve targeted photothermal/catalytic combination therapy. Firstly, L-arginine (L-Arg) and glucose oxidase (GOx) were loaded onto HCNPNs to obtain HCNPNs/AG. Then, they were functionalized with an aptamer (Apt) to obtain a multifunctional nanozyme. The constructed HCNPNs/AGPM possessed multienzyme-like activities, including GOx-like, peroxidase (POD)-like and nitric oxide synthase (NOS)-like catalytic activities, which enabled the multifunctional nanozyme to generate sufficient hydroxyl radicals (•OH) and NO for catalytic therapy. Moreover, this multifunctional nanozyme displayed outstanding photothermal-conversion activity for photothermal therapy (PTT) upon 808 nm laser irradiation because of the strong light absorption capacity of HCNPNs. Notably, the multifunctional nanozyme showed enhanced cytotoxicity in MCF-7 cells, benefiting from the specific recognition ability of Apt. The results of in vitro and in vivo experiments revealed that HCNPNs/AGPM could eliminate tumors without apparent side effects. Consequently, the constructed multifunctional nanozyme may provide a hopeful paradigm for tumor-targeted therapy and inspire the further development of nanozymes in clinical trials.