Abstract

Despite an ever-growing number of investigations and advances in nanozymes and oxidative stress anti-tumor therapy, nanoparticles capable of maintaining the redox balance as natural antioxidative system are scarce. Herein, iron phosphates -based (FePOs) nanozyme, was synthesized via a simple hydrothermal method. We first discovered that the FePOs nanozyme has trienzyme-like activities. It is peroxidase (POD)-like in acidic tumor microenvironment and can mediate a highly efficient FePOs + H 2 O 2 anti-tumor protocol via catalyzing ·OH generation from H 2 O 2 . Quite different from any other reported nanozymes, at physiological pH the FePOs is not only catalase (CAT)-like but also superoxide dismutase (SOD)-like. It exerts combined SOD-CAT effects on normal tissues, which is analogous to the synergistic effects of natural SOD-CAT in living organisms, and hence protects normal tissues from injuries of the FePOs + H 2 O 2 protocol. Apoptosis was found to be the pathway by which cancer cell death is induced by FePOs + H 2 O 2 . Notably, the FePOs + H 2 O 2 protocol led to no abnormal behavior, significant weight loss or obvious adverse effects on normal tissues in mice as the results of the combined SOD-CAT effects. All these intriguing results confirm that the FePOs nanozyme is an excellent candidate for nanomedicine and holds promise for enhanced anti-tumor efficiency with minimal side effects.