A Target-Induced In Situ J-Aggregation Coupling Cascade Catalyzing Reactive Oxygen Species Clearance Strategy for 3D NIR-II Photoacoustic Imaging Diagnosis and Smart Therapy of Acute Kidney Injury

Acute kidney injury (AKI) is a prevalent complication among hospitalized patients and is characterized by high mortality rates. Despite advancements in treatment strategies, early diagnosis and effective management of AKI remain significant challenges in clinical medicine. Herein, we present a target-induced in situ J-aggregation coupling cascade catalyzing reactive oxygen species (ROS) clearance strategy and developed a nanodiagnostic-therapeutic agent Cu-POW@Apt-CY@SC (CPACSC) for 3D near-infrared II (NIR-II) photoacoustic (PA) imaging diagnosis and smart therapy of AKI. Upon intravenous administration, CPACSC targets renal tubular epithelial cells via interaction with kidney injury molecule-1 (Kim-1), then binds to neutrophil gelatinase-associated lipid carrier protein (NGAL), releasing CY-1005 molecules and undergo in situ NIR-II J-aggregation, affording precise 3D multispectral PA imaging diagnosis of AKI. CPACSC exhibits also superoxide dismutase (SOD) and catalase (CAT) activities, an in situ cascade catalyzing the conversion of O₂^•- and H₂O₂ into O₂, thereby cleaning up ROS in injured renal tissues and affording targeted therapy. These findings underscore CPACSC as a nanodiagnosis and treatment integrated platform for AKI, achieving precision medicine through target-induced in situ NIR-II J-aggregation and cascade catalyzing ROS clearance, thereby offering a strategy for AKI disease management.