Degradable Fe3O4-based nanocomposite for cascade reaction-enhanced anti-tumor therapy

Cascade catalytic therapy has been recognized as a promising cancer treatment strategy, which is due in part to the induced tumor apoptosis when converting intratumoral hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (OH) based on the Fenton or Fenton-like reactions. Moreover this is driven by the efficient catalysis of glucose oxidization associated with starving therapy. The natural glucose oxidase (GO(x)), recognized as a star enzyme catalyst involved in cancer treatment, can specially and efficiently catalyze the glucose oxidization into gluconic acid and H2O2. Herein, pH-responsive biodegradable cascade therapeutic nanocomposites (Fe3O4/GO(x)-PLGA) with dual enzymatic catalytic features were designed to respond to the tumor microenvironment (TME) and to catalyze the cascade reaction (glucose oxidation and Fenton-like reaction) for inducing oxidase stress. The GO(x)-motivated oxidation reaction could effectively consume intratumoral glucose to produce H2O2 for starvation therapy and the enriched H2O2 was subsequently converted into highly toxic OH by a Fe3O4-mediated Fenton-like reaction for chemodynamic therapy (CDT). In addition, the acidity amplification owing to the generation of gluconic acid will in turn accelerate the degradation of the nanocomposite and initiate the Fe3O4-H2O2 reaction for enhancing CDT. The resultant cooperative cancer therapy was proven to provide highly efficient tumor inhibition on HeLa cells with minimal systemic toxicity. This cascade catalytic Fenton nanocomposite might provide a promising strategy for efficient cancer therapy.

Automated summary

Cascade catalytic therapy is a promising cancer treatment strategy that induces tumor apoptosis by converting intratumoral H2O2 into highly toxic OH radicals. In this study, pH-responsive biodegradable nanocomposites with dual enzymatic catalytic features were designed to respond to the tumor microenvironment and catalyze glucose oxidation and the Fenton-like reaction for inducing oxidative stress. The cooperative cancer therapy showed highly efficient tumor inhibition on HeLa cells with minimal systemic toxicity.