A flowerlike FePt/MnO₂/GOx-based cascade nanoreactor with sustainable O₂ supply for synergistic starvation-chemodynamic anticancer therapy

Abstract

The development of versatile nanotheranostic agents has received increasing interest in cancer treatment. Herein, in this study, we rationally designed and prepared a novel flowerlike multifunctional cascade nanoreactor, BSA-GOx@MnO₂@FePt (BGMFP), by integrating glucose oxidase (GOx), manganese dioxide (MnO₂) and FePt for synergetic cancer treatment with satisfying therapeutic efficiency. In an acidic environment, intratumoral H₂O₂ could be decomposed to O₂ to accelerate the consumption of glucose catalyzed by GOx to induce cancer starvation. Moreover, the accumulation of gluconic acid and H₂O₂ generated along with the consumption of glucose would in turn promote the catalytic efficiency of MnO₂ and boost O₂ evolution, which could enhance the efficiency of starvation therapy. Moreover, FePt as an excellent Fenton agent could simultaneously convert H₂O₂ to the toxic hydroxyl radical (˙OH), subsequently resulting in amplified intracellular oxidative stress and cell apoptosis. Therefore, BGMFP could catalyze a cascade of intracellular biochemical reactions and optimize the unique properties of MnO₂, GOx and FePt <i>via</i> mutual promotion of each other to realize O₂ supply, chemodynamic therapy (CDT) and starvation therapy. The anticancer results <i>in vitro</i> and <i>in vivo</i> demonstrated that BGMFP possessed remarkable tumor inhibition capacity through enhancing the starvation therapy and CDT. It is appreciated that BGMFP could be a promising platform for synergetic cancer treatment.