Sulfite-Inserted MgAl Layered Double Hydroxides Loaded with Glucose Oxidase to Enable SO2-Mediated Synergistic Tumor Therapy

As a type of unique gaseous molecules, SO2 presents capabilities in the feasible cellular influx and the induction of apoptosis by generating intracellular toxic radicals. Developing therapeutic platforms to enable effective SO2 gas release at the tumor site is highly demanded in the exploration of more "green" and effective treatment protocols for cancer therapy but remains challenging. Here for the first time, fine nanosheets composing of Mg-Al layered double hydroxides (MgAl LDH) are synthesized and inserted with sulfite in its layered structures (MgAl-SO3 LDH). After the loading of glucose oxidase (GOx/MgAl-SO3 LDH), the composite nanosheets present the controllable SO2 gas release in an acidic responsive manner. Owing to the glycolysis effect of GOx, the gluconic acid generated agitates the intracellular SO2 release from nanosheets, and excessive H2O2 reacts with SO2 effectively and facilitates the production of toxic radicals, inducing remarkable oxidative damages to tumor cells. Meanwhile, the consumption of intracellular glucose by GOx/MgAl-SO3 LDH depletes the energy supply of tumor cells, favoring the tumor inhibition both in vitro and in vivo in a synergistic fashion. Therefore, this study has provided distinctive perspectives in the exploration of therapeutic platforms with green functionalities and biodegradability for effective tumor treatment.