Glucose oxidase (GOX) can convert glucose into gluconic acid and hydrogen peroxide (H2O2), which is potentially useful for synergistic cancer-starving and oxidation therapy. Herein we demonstrate a glucose-responsive nanomedicine made of GOX-polymer nanogels to regulate H2O2 production for synergistic melanoma starving and oxidation therapy. GOX-polymer nanogels showed glucose-responsive H2O2-generating activity in vitro, improved stability, and considerably enhanced tumor retention as compared to native GOX. More importantly, they exhibited high antimelanoma efficacy and no obvious systemic toxicity, whereas native GOX was ineffective and systemically toxic at the same dose. This work paves the way for establishing an endogenous and noninvasive cancer treatment paradigm that is based on intratumoral glucose-responsive, H2O2-generating chemical reactions.
Keywords: cancer therapy; glucose oxidase; nanogel; protein−polymer conjugate; synergistic therapy.