Degradable Fe(3)O(4)-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 (H(2)O(2)) 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 H(2)O(2). Herein, pH-responsive biodegradable cascade therapeutic nanocomposites (Fe(3)O(4)/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 H(2)O(2) for starvation therapy and the enriched H(2)O(2) was subsequently converted into highly toxic ˙OH by a Fe(3)O(4)-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 Fe(3)O(4)–H(2)O(2) 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.