Kim-1 Targeted Black Phosphorus Nanoplatforms: Antioxidation and Efferocytosis Recovery for AKI Treatment

Background: Acute kidney injury (AKI) is a global public health issue with high morbidity and mortality rates. Past research on AKI treatment has predominantly focused on antioxidation and anti-inflammation, with little attention given to the clearance of apoptotic cells post-AKI. The clearance of apoptotic cells, or efferocytosis, is crucial for resolving inflammation. However, the inflammation triggered by oxidative stress in the damaged tissue region of AKI often impedes efferocytosis, hindering the clearance of apoptotic cells and exacerbating inflammation, thereby causing tissue damage. Methods: In this study, we designed a kidney dual-targeted nanotherapy platform utilizing the Kim-1 protein-targeting peptide LTH combined with the therapeutic agent 4-octyl itaconate (4OI), based on novel two-dimensional black phosphorus nanosheets,to treat AKI induced by various etiologies. Results: The nanoplatform rapidly anchors to damaged renal tubular epithelial cells, clearing intracellular ROS overload, thereby reducing tubular dilation and inhibiting cast formation. Following intervention, the expression of NGAL in the kidneys of AKI mice significantly decreases, indicating substantial alleviation of tissue damage. Moreover, the improvement in efferocytosis facilitates the clearance of apoptotic cells, effectively mitigating renal tissue injury following rhabdomyolysis and renal ischemia-reperfusion injury. Conclusion: The novel kidney dual-targeted nanoplatform achieves rapid targeting and anchoring to damaged renal tubular epithelial cells post-AKI. Through antioxidative stress and enhancement of efferocytosis, it enables specific treatment of AKI in the affected regions. We believe this platform presents a new solution for AKI treatment induced by various causes and holds promise as an innovative drug delivery system for the treatment of other diseases. Funding: Government Support – Non-U.S.