Ru@MnO 2 hybrid nanozymes catalyze H 2O 2 to produce oxygen to relieve tumor hypoxia, and then enhance photothermal therapy and chemotherapy.
Hypoxia in the solid tumor microenvironment (TME) can easily induce tumor recurrence, metastasis, and drug resistance. The use of man-made nanozymes is considered to be an effective strategy for regulating hypoxia in the TME. Herein, Ru@MnO 2 nanozymes were constructed via an in situ reduction method, and they showed excellent photothermal conversion efficiency and catalytic activity. The anti-tumor drug DOX with fluorescence was loaded on the Ru@MnO 2 nanozymes, and an erythrocyte membrane was further coated on the surface of the Ru@MnO 2 nanozymes to construct nanozymes with on-demand release abilities. The erythrocyte membrane (RBCm) enhances the biocompatibility of the Ru@MnO 2 nanozymes and prolongs their circulation time in the blood. Ru@MnO 2 nanozymes can catalyze endogenous H 2O 2 to produce O 2 to relieve hypoxia in the TME to enhance the efficacy of the photothermal therapy/chemotherapy of cancer. In vitro studies confirmed that the Ru@MnO 2 nanozymes showed good tumor penetration abilities and a synergistic anti-tumor effect. Importantly, both in vivo and in vitro studies have confirmed that the oxygen supply in situ enhanced the efficacy of the PTT/chemotherapy of cancer. Accordingly, this study demonstrated that Ru@MnO 2 nanozymes can be used as an effective integrated system allowing catalysis, photothermal therapy, and chemotherapy for cancer management.