Engineered renal-targeting nanozyme achieves sequential treatment of AKI through ROS clearance and immune modulation

Effective countermeasures for acute kidney injury (AKI) remain unsatisfactory. During AKI progression, the timely and appropriate transition of macrophages from pro-inflammatory to anti-inflammatory states is critical for resolving acute inflammation and promoting tissue repair. Timely clearing of excess reactive oxygen species (ROS) and promotion of M2 polarization of macrophages are key determinants of AKI progression. Accordingly, we report an engineered renal-targeting nanozyme constructed from a novel two-dimensional nanomaterial, MXene nanosheets, via surface conjugation of the anticomplement component 5a aptamer (ac5a-Apt) and magnesium ions (Mg^2 +). After AKI, the engineered nanozyme can not only target the kidneys but also navigates to inflammatory areas under the guidance of the ac5a-Apt, clear excessive ROS, inhibits 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, further suppressing the MAPK/ NF-κB signaling pathway to achieve sequential therapy. The engineered renal-targeting nanozyme offers a novel strategy based on ROS clearance and immune modulation for sequential AKI treatment.