Renal-targeting bioinspired curcumin framework nanozyme for regulating inflammatory and oxidative stress homeostasis in acute kidney injury

• We developed a curcumin framework nanozyme that enhances antioxidant and anti-inflammatory activities synergistically. • The synthesized PL@Cur-MnZn nanozyme showed enhanced renal-targeted therapy and clinical translation efficiency. • PL@Cur-MnZn alleviates renal acute kidney injury by promoting Nrf2 activation and reducing mitochondrial oxidative stress. Kidney ischemia–reperfusion injury (IRI) is a common and unavoidable pathological condition in transplantation, characterized by elevated levels of endogenous reactive oxygen species (ROS) and inflammation. However, drugs with only antioxidant or anti-inflammatory properties are often insufficient to effectively alleviate IRI. In this study, we developed a platelet membrane-coated curcumin framework nanozyme (PL@Cur-MnZn) that exhibits enhanced antioxidant and anti-inflammatory activities compared to curcumin or Mn-ZIF alone, due to the synergistic effects of the incorporated active agents. The natural affinity of platelets endows PL@Cur-MnZn with efficient renal targeting ability, leveraging the homing properties of platelets. These particles demonstrated significant cytoprotective effects and reduced kidney IRI both in vitro and in vivo, without noticeable toxicity. This was achieved by inhibiting cell apoptosis and enhancing Nrf2 activation, which in turn activates the endogenous Nrf2-Keap1-ARE signaling pathway. This leads to synergistic antioxidant effects from both external and internal sources, further alleviating renal IRI. Therefore, PL@Cur-MnZn holds potential as an effective therapeutic agent for managing kidney IRI and could contribute to advancing clinical treatment strategies for this condition.