Cutting off the energy supply by
glucose oxidase (GOx) to starve
cancer cells has been a feasible and efficient oncotherapy strategy. The employment of GOx can effectively starve
tumor cells by aerobic hydrolysis of
glucose hopefully strengthening the abnormality (including the decrease in pH, the increase of
hypoxia, and toxic
hydrogen peroxide) in the tumor microenvironment (TME). On this basis, we designed and fabricated a GOx-conjugated yolk-shell Ag@mSiO2 nanoframe with Ag NPs and GOx-conjugated mesoporous
silica as the yolk and the shell, respectively, to make full use of changes the GOx induces in TME. Specifically, lower pH and H2O2 could accelerate the transformation of Ag nanoparticles to poisonous Ag
ions. At the same time, the anabatic
hypoxia condition in turn activated
chemotherapy drug tirapazamine (TPZ) to exert a chemotherapeutic effect, thereby achieving effective chemo/
starvation and
metal ion multimodality
therapy. The drug release experiment in vitro demonstrated that the GOx is the key to the nanocarriers, which can activate the whole system. The excellent cellular uptake performances of nanocarriers were corroborated by a confocal
laser scanning microscope (CLSM). In addition, its superb
cancer-killing effect has been confirmed by cytotoxicity and apoptosis experiments. These results indicated that the drug-delivery system achieved the cascade
cancer-killing process in situ and synergistic chemo/
starvation/
metal ion
therapy, which has a bright prospect for treating
cancer.