Glucose-Responsive Sequential Generation of Hydrogen Peroxide and Nitric Oxide for Synergistic Cancer Starving-Like/Gas Therapy

Glucose is a key energy supplier and nutrient for tumor growth. Herein, inspired by the glucose oxidase (GOx)assisted conversion of glucose into gluconic acid and toxic H2O2, a novel treatment paradigm of starving- like therapy is developed for significant tumor- killing effects, more effective than conventional starving therapy by only cutting off the energy supply. Furthermore, the generated acidic H2O2 can oxidize l- Arginine (l- Arg) into NO for enhanced gas therapy. By using hollow mesoporous organosilica nanoparticle (HMON) as a biocompatible/biodegradable nanocarrier for the co-delivery of GOx and l- Arg, a novel glucose- responsive nanomedicine (l- Arg- HMON- GOx) has been for the first time constructed for synergistic cancer starving- like/gas therapy without the need of external excitation, which yields a remarkable H2O2-NO cooperative anticancer effect with minimal adverse effect.