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

For catalytic nanozyme and biomaterials in disease treatment, the iron-based catalysts suffer from low center dot 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 center dot 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.

Automated summary

A polymetallic Cu0.5Mn0.5Fe2O4 (CMF) nanozyme has been engineered to generate a large amount of center dot OH, amplify reactive oxygen species production, elevate oxidative stress level and induce cell pyroptosis. Exogenous ultrasound irradiation further amplifies and improves therapeutic effect in treating lung cancer.