A Membrane-Fused Theranostic Nanoplatform for Real-Time ROS Imaging and Mitochondrial Resuscitation-Driven Barrier Repair in Acute Kidney Injury

Effective management of Acute Kidney Injury (AKI) is currently limited by the lack of unified platforms capable of simultaneous diagnosis and structural repair. Addressing this challenge, a biomimetic theranostic nanoplatform, Lipoic Acid-loaded Exosome-Like Nanoparticles (EXLNPs), was engineered via a membrane fusion strategy wherein the homing capability of MSC-derived (Mesenchymal Stem Cells-derived) exosomes is synergized with the high-loading efficiency of synthetic liposomes. Upon administration, EXLNPs acted as a self-reporting diagnostic agent, exhibiting real-time fluorescence activation in response to high-ROS microenvironments, which correlated accurately with injury severity. Therapeutically, the membrane-fused EXLNPs outperformed native exosomes by orchestrating a precision "detect-and-repair" cascade. They effectively scavenged ROS to reverse mitochondrial metabolic collapse, thereby restoring the oxidative phosphorylation capacity and ATP production essential for the energy-dependent re-assembly of epithelial tight junctions (Occludin 1 and 15, CLDN1 and 15). This restoration of the mitochondrial-barrier axis significantly ameliorated tubular necrosis and recovered renal function in ischemic AKI models. These findings demonstrate that this bio-synthetic hybrid strategy offers a potent, clinically relevant solution for the precision diagnosis and metabolic reprogramming of acute renal diseases.