), we identified Mn-chelating L-serine (L-SerMn) as the optimal nanoarchitecture, displaying robust superoxide dismutase (SOD)- and catalase (CAT)-like activities. Molecular dynamics simulations revealed stronger binding affinity of L-SerMn to Kim-1 compared to free L-serine. In vitro, L-SerMn protected renal tubular epithelial cells from hypoxia/reoxygenation (H/R)-induced damage by functioning as a dual SOD/CAT mimic. In vivo, L-SerMn achieved selective accumulation in injured kidneys via Kim-1-mediated targeting, enabling sustained restoration of redox homeostasis that ameliorated renal pathological injury. Mechanistically, L-SerMn ameliorated renal I/R injury and blocked the acute kidney injury (AKI)-chronic kidney disease (CKD) transition via suppression of cellular senescence, through regulating the JAK2-STAT3 and p53 signaling pathways. This work elegantly integrates coordination chemistry and biomimetic enzymology for the rational design of organ-targeted nanotherapeutics, offering a promising strategy against ischemic diseases.
Li et al. (Fri,) studied this question.
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