Renal tubular epithelial cell (RTEC) is a critical target cell for the treatment of acute kidney injury (AKI). Despite various RTEC targeting strategies using ligand modified nanoparticles (NPs) following systemic administration, the nonspecific interaction between NPs and plasma proteins greatly weakens the targeting efficiency as well as the stability of NPs. Herein, celastrol (CLT) was entrapped in D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) forming a CLT-loaded nanocomplex core (CT) with a high loading capacity of ~50%. Bovine serum albumin (BSA) was then adsorbed onto the CT surface to afford a complete albumin corona without obvious denaturation (CTB). CTB showed uniform particle size distribution and sufficient stability in vitro and in vivo. Besides clathrin-mediated and macropinocytosis pathways, CTB was actively internalized through megalin receptor-mediated endocytosis in HK-2 cells. Per biodistribution studies, CTB demonstrates enhanced renal tubule-specific distribution and targetability in mice compared to CT without albumin corona. Furthermore, pharmacodynamic studies in vivo further support that CTB effectively alleviated ischemia-reperfusion induced injuries without obvious systemic side effects in AKI mice models.

肾小管上皮细胞 (RTEC) 是治疗急性肾损伤 (AKI) 的关键靶细胞。尽管在全身给药后使用配体修饰的纳米粒子 (NPs) 的各种 RTEC 靶向策略，但 NPs 和血浆蛋白之间的非特异性相互作用大大削弱了靶向效率以及 NPs 的稳定性。在此，celastrol (CLT) 被包裹在 D-α-生育酚聚乙二醇 1000 琥珀酸酯 (TPGS) 中，形成负载 CLT 的纳米复合物核心 (CT)，具有约 50% 的高负载能力。然后将牛血清白蛋白 (BSA) 吸附到 CT 表面上以提供完整的白蛋白电晕而没有明显的变性 (CTB)。CTB在体外和体内表现出均匀的粒度分布和足够的稳定性. 除了网格蛋白介导的和巨胞饮作用途径外，CTB 通过巨蛋白受体介导的 HK-2 细胞内吞作用被积极内化。根据生物分布研究，与没有白蛋白电晕的 CT 相比，CTB 在小鼠中表现出增强的肾小管特异性分布和靶向性。此外，体内药效学研究进一步支持 CTB 有效缓解缺血再灌注诱导的损伤，而在 AKI 小鼠模型中没有明显的全身副作用。