Mesoporous peroxidase nanozyme for synergistic chemodynamic therapy and chemotherapy

Peroxidase nanozyme, enabling decomposition of hydrogen peroxide (H2O2) into highly toxic hydroxyl radical ((OH)-O-center dot), is an emerging technology for tumor treatment. However, limited by the low H2O2 level in the tumor microenvironment, the standalone peroxidase nanozyme-mediated therapy usually fails to achieve desirable therapeutic outcomes. Herein, we presented a mesoporous nanozyme that not only had peroxidase-like activity but also could deliver anticancer drug for synergistic tumor therapy. The nanozyme, that was, iron-doped mesoporous silica nanoparticle (FeMSN), was prepared by a sol-gel method and then a calcination treatment. The introduction of iron endowed FeMSN with peroxidase-like activity that could decompose H2O2 into (OH)-O-center dot under acidic condition for chemodynamic therapy of tumors. Meanwhile, the mesoporous structure enabled FeMSN to deliver anticancer drug doxorubicin (DOX) for chemotherapy and enhanced chemodynamic therapy through H2O2 production, ultimately achieving synergistic effect to improve the efficacy of tumor treatment. The in-vitro and in-vivo results demonstrated that DOX-loaded FeMSN exhibited significant cancer cell-killing effect and potently inhibited tumor growth. Collectively, this study represented a paradigm for achieving efficient tumor therapy through design of peroxidase-like nanozyme with drug delivery capability, which might advance the development of nanozyme in tumor chemodynamic therapy.