TGase-Induced Covalent Enrichment of Gold Nanoclusters with Spatial-Arrangement Dependence of Peptides for In Vivo Diagnosis of Acute Kidney Injury.

Near-infrared-II (NIR-II) emissive gold nanoclusters (AuNCs) have garnered significant attention for fluorescence imaging owing to their excellent biocompatibility. However, achieving highly specific imaging at lesion sites remains a challenge. Herein, we constructed a peptide-modified NIR-II luminescent AuNCs probe (AuNCs-Q&K) for specific imaging of acute kidney injury by leveraging the covalent cross-linking properties of transglutaminase (TGase), an enzyme significantly upregulated in acute kidney injury (AKI). The TGase enzyme enables the recognition of peptide sequences containing glutamine (Q) and lysine (K) to covalently form isopeptide bonds in a spatial-arrangement dependent manner, thereby triggering in situ aggregation of probes. In a cisplatin-induced AKI mouse model, AuNCs-Q&K specifically respond to the overexpressed TGase at the injured sites, driving localized retention and a significantly prolonged imaging. This work presents a novel strategy for noninvasive long-term monitoring of AKI and expands the application of enzymatic in situ assembly of AuNCs.