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 via mutual promotion of each other to realize O₂ supply, chemodynamic therapy (CDT) and starvation therapy. The anticancer results in vitro and in vivo 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.