Surface-cleaned black phosphorus nanosheets chelate iron and rebalance the ferroptosis-immune axis in acute kidney injury

作者：Tan WL, Zhu JM, Xu XX, Jia J, Chen RY, Yu X, Liang LQ, Ruan YY, Wang FF, Chen YT, Peng YL, Peng J, Wang D, Liu LL, Ran Y, Guo B, Feng J, Wang YY · 发表于：Theranostics · 年份：2026 · DOI：10.7150/thno.129807 · 被引用次数：48 · 研究领域：Acute Kidney Injury、Ferroptosis、Nanostructures、Iron、Phosphorus、Iron Chelating Agents、Animals、Mice、Oxidative Stress、Epithelial Cells、Male、Reactive Oxygen Species

RATIONALE: Nanomaterials have been explored for acute kidney injury (AKI) therapy because of their ability to scavenge reactive oxygen species (ROS) and reduce oxidative stress. Black phosphorus nanosheets (BPNSs) show renoprotective potential, but spontaneous surface oxidation may weaken their redox activity and therapeutic efficacy. It remains unclear whether surface engineering can improve the biological activity of BPNSs and modulate ferroptosis and immune activation during AKI. METHODS: Surface-cleaned BPNSs (sc-BPNSs) were prepared by hydrogen reduction and characterized. Fluorescence-labeled sc-BPNSs were used to examine biodistribution, and therapeutic efficacy was evaluated in mice with AKI. In vitro, mouse renal tubular epithelial cells (mRTECs) were subjected to hypoxia/reoxygenation (H/R). Ferroptosis and iron homeostasis were assessed using biochemical, histological, and imaging assays. RNA sequencing was performed in mRTECs and macrophages to identify pathways affected by sc-BPNSs. A tubular epithelial cell-macrophage co-culture model was used to examine intercellular crosstalk after injury. RESULTS: Hydrogen reduction produced sc-BPNSs with reduced surface oxidation, stronger antioxidant activity, and improved renal accumulation. After intravenous administration, sc-BPNSs preferentially accumulated in injured kidneys, reduced ROS accumulation and lipid peroxidation, alleviated tubular injury, and improved renal function. Transcriptomic analysis showed that sc...