Diagnostic and therapeutic nanoenzymes for enhanced chemotherapy and photodynamic therapy

Nanozymes, as a kind of artificial mimic enzymes, have superior catalytic capacity and stability. As lack of O 2 in tumor cells can cause resistance to drugs, we designed drug delivery liposomes (MnO 2 -PTX/Ce6@lips) loaded with catalase-like nanozymes of manganese dioxide nanoparticles (MnO 2 NPs), paclitaxel (PTX) and chlorin e6 (Ce6) to consume tumor's native H 2 O 2 and produce O 2 . Based on the catalysis of MnO 2 NPs, a large amount of oxygen was produced by MnO 2 -PTX/Ce6@lips to burst the liposomes and achieve a responsive release of the loaded drug (paclitaxel), and the released O 2 relieved the chemoresistance of tumor cells and provided raw materials for photodynamic therapy. Subsequently, MnO 2 NPs were decomposed into Mn 2+ in an acidic tumor environment to be used as contrast agents for magnetic resonance imaging. The MnO 2 -PTX/Ce6@lips enhanced the efficacy of chemotherapy and photodynamic therapy (PDT) in bearing-tumor mice, even achieving complete cure. These results indicated the great potential of MnO 2 -PTX/Ce6@lips for the modulation of the TME and the enhancement of chemotherapy and PDT along with MRI tracing in the treatment of tumors. We creatively designed a nanodrug delivery system of MnO 2 -PTX/Ce6@lips based on the catalytic activity of MnO 2 NPs. We synthesized a highly dispersible catalase-like nanozyme and successfully encapsulated it into liposomes.