A Dual-Response DNA Origami Platform for Imaging and Treatment of Sepsis-Associated Acute Kidney Injury

Abstract

Current diagnostics for sepsis-associated acute kidney injury (SA-AKI) detect kidney damage only at advanced stages, limiting opportunities for timely intervention. A DNA origami-based nanoplatform is developed for the early diagnosis and treatment of SA-AKI. Modified with a fluorophore (Cy5) and quencher (BHQ3), the DNA origami remains nonfluorescent under normal conditions. During SA-AKI, elevated microRNA-21 triggers a strand displacement reaction that restores the fluorescence signal, enabling real-time detection. Additionally, the photoacoustic changes of BHQ3, driven by different excretion rates of the nanostructure and released DNA strands, enable dual-mode imaging, enhancing diagnostic accuracy. Therapeutically, DNA origami scavenges reactive oxygen species and, when conjugated with the antimicrobial peptide Leucine-Leucine-37 (LL-37), exhibits bactericidal effects. This combination boosts survival rates by 80% in SA-AKI models. This dual-response nanoplatform integrates precise imaging and targeted therapy, offering a powerful strategy for SA-AKI management and advancing applications of DNA origami in precision nanomedicine.

Keywords: DNA origami; dual‐modal imaging; reactive oxygen species; sepsis‐associated acute kidney injury.