Ultrasound-amplified polymetallic nanozyme-induced pyroptosis for lung cancer theranostics

Abstract

For catalytic nanozyme and biomaterials in disease treatment, the iron-based catalysts suffer from low •OH generation performance due to the creation of a passive Fe (III) oxide layer and the prevention of the catalytic activation of H2O2 as a result of the oxidation of Fe (II) to Fe (III). Herein, polymetallic Cu0.5Mn0.5Fe2O4 (CMF) nanozyme has been rationally designed and engineered for massive generation of •OH through stabilizing the surface ferric species and providing enormous catalytically active sites. Furthermore, such a nanozyme with multienzyme-mimicking activities can amplify the reactive oxygen species production, elevate the oxidative stress level and induce cell pyroptosis. Importantly, exogenous ultrasound irradiation further achieves the goal of amplified and precise therapeutic effect again lung cancer. The in vitro and in vivo anti-tumor theranostic results confirm the accurate T1-T2 dual-mode magnetic resonance imaging and emphatic tumor inhibition effect of ultrasound-amplified CMF nanozymes. These results provide the paradigm of the utilization of polymetallic nanozymes as a therapeutic nanoplatform in treating apoptosis-resistant and pyroptosis sensitive tumors.