The restriction of a
tumor's energy supply is proven to be an effective means of treatment.
Glucose oxidase (GOx), an
enzyme that catalyzes the conversion of
glucose to glucolactone, producing
oxygen and
hydrogen peroxide in the process, has proved useful in this regard. However,
hypoxia, which is implicated in
tumor growth, has been found to mediate resistance to this type of
tumor starvation. Here, we describe the design and testing of a platelet membrane mimetic, PMS, consisting of mesoporous
silica nanoparticles (MSNs) loaded with
metformin (MET) as an inner layer and platelet membranes (PM) as an outer layer that inhibits oxygen consumption by the
tumor cells' respiratory pathways and enhances the effectiveness of GOx. MET directly inhibits the activity of complex I in mitochondrial electron transport and is thus a potent inhibitor of cell respiration. PMS target
tumor tissue effectively and, once internalized, MET can inhibit respiration. When
oxygen is plentiful, GOx promotes
glucose consumption, allowing amplification of its effects on
tumor starvation. This combination of respiratory suppression by PMS and
starvation therapy by GOx has been found to be effective in both targeting
tumors and inhibiting their growth. It is hoped that this strategy will shed light on the development of next-generation
tumor starvation treatments.