Mesoporous Silica-Coated Silver Nanoframes as Drug-Delivery Vehicles for Chemo/Starvation/Metal Ion Multimodality Therapy

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Abstract
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 effectively starves tumor cells by aerobic hydrolysis of glucose, and in turn reconstitutes the tumor microenvironment (TME) by strengthening the abnormality (including the decrease of the pH, the increase of hypoxia and toxic hydrogen peroxide). On this basis, we designed and fabricated a GOx-conjugated yolk-shell [email protected] nanoframes with Ag NPs and GOx-conjugated mesoporous silica as yolk and shell respectively, to make full use of changes in TME the GOx brings. Specially, the lower pH and the generation of H2O2 could accelerate the transform of Ag nanoparticles to poisonous Ag ions. At the same time, the anabatic hypoxia condition in turn activated chemotherapy drug tirapazamine (TPZ) to play a chemotherapeutic effect, thereby achieving effective multimodality therapy (Chemo/Starvation and metal ions). The drug release experiment in vitro demonstrated that the GOx is the key of the nano carriers which can activate the whole system. Its excellent cellular uptake performances were obtained by Confocal Laser Scanning Microscope (CLSM). In addition, its superb cancer killing effect has been confirmed by the cytotoxicity and apoptosis experiments. These results indicated that the drug delivery system achieved the cascade cancer killing progress in situ and synergistic chemo/metal ions/starvation therapy, which have a bright prospect for treating cancer.
Funding Information
  • Ministry of Science and Technology of the People's Republic of China (2015DFG42240)
  • National Natural Science Foundation of China (21371031, 21628101)
  • Priority Academic Program Development of Jiangsu Higher Education Institutions

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