Engineered Renal-Targeting Nanozyme Achieves Sequential Treatment of AKI through Reactive Oxygen Species Clearance and Immune Modulation

Background: Effective countermeasures for acute kidney injury (AKI) remain unsatisfactory. During AKI progression, the appropriate and timely transition of macrophages from pro-inflammatory to anti-inflammatory states is crucial for promoting the resolution of acute inflammation and tissue repair. Timely clearing excess reactive oxygen species (ROS) and promoting M2 polarization of macrophages determines the extent of AKI progression. Methods: In this study, we designed an engineered renal-targeting nanozyme constructed from a novel two-dimensional nanomaterial, MXene nanosheets, through surface conjugation of the anticomplement component 5a aptamer (ac5a-Apt) and magnesium ions (Mg2+). Results: The results revealed that after AKI, the engineered nanozyme can not only target the kidneys but also navigate towards inflammatory areas under the guidance of the ac5a-Apt, clear excessive ROS, inhibit the C5a-C5aR complement system activation and promote M2 polarization of macrophages. Importantly, after MXene reacts with ROS and degrades, the surface-loaded Mg2+ is released, which can further suppress the MAPK/ NF-κB signaling pathway to achieve sequential therapy. Conclusion: The engineered renal-targeting nanozyme provides a novel strategy based on ROS clearance and immune modulation for AKI sequential treatment. And as a novel engineered nanozyme, its remarkable biocompatibility and excellent therapeutic effectiveness establish the foundation for its substantial potential in clinical translation. Funding: Government Support – Non-U.S.