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

Abstract

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 H₂ O₂ , 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 H₂ O₂ 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 H₂ O₂ -NO cooperative anticancer effect with minimal adverse effect.

Keywords: hydrogen peroxide; mesoporous nanomaterials; nitric oxide; synergistic therapy; ultrasound imaging.