Diagnostic and therapeutic nanoenzymes for enhanced chemotherapy and photodynamic therapy

Abstract

Nanozymes, as a kind of artificial mimic enzymes, have superior catalytic capacity and stability. As lack of O₂ in tumor cells can cause resistance to drugs, we designed drug delivery liposomes (MnO₂-PTX/Ce6@lips) loaded with catalase-like nanozymes of manganese dioxide nanoparticles (MnO₂ NPs), paclitaxel (PTX) and chlorin e6 (Ce6) to consume tumor's native H₂O₂ and produce O₂. Based on the catalysis of MnO₂ NPs, a large amount of oxygen was produced by MnO₂-PTX/Ce6@lips to burst the liposomes and achieve a responsive release of the loaded drug (paclitaxel), and the released O₂ relieved the chemoresistance of tumor cells and provided raw materials for photodynamic therapy. Subsequently, MnO₂ NPs were decomposed into Mn²⁺ in an acidic tumor environment to be used as contrast agents for magnetic resonance imaging. The MnO₂-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 MnO₂-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.