DNA-Engineered Dual-Signal Biomimetic Fusion Vesicles for Rapid Evaluation of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a rare autoimmune disease with complex and variable clinical presentations that affects numerous organs and tissues. However, current diagnostic approaches provide limited insight into disease-associated molecular alterations and immune pathway activation. In this work, we report an exosome-capture-based system for rapid detection of SLE by the integration of functional DNA structures and lipid vesicles to form dual-signal biomimetic fusion vesicles (DBFVs). DBFVs are constructed by liposomes composed of DOPC, DPPC, and cholesterol, which are further functionalized with a sialic acid (SA)-binding aptamer at the outer surface to promote specific exosome capture and membrane fusion. At the same time, a DNA probe enabling dual-signal response of Mn 2+ and miRNA-146a is encapsulated in DBFVs. With SA-binding aptamer equipped on the surface, DBFVs can easily capture and fuse with SA-expressed exosomes in clinical samples. After enrichment of DBFV-exosome hybrid vesicles on latex beads, the DNA probe inside the vesicle can report the expression of Mn 2+ and miRNA-146a by dual-channel fluorescence readout to evaluate the activation level of the cGAS–STING pathway. Our system shows high efficiency and accuracy in differentiating SLE patients and healthy donors by testing plasma and urine samples without complex gradient centrifugation. The practicality of DBFVs provides a practical tool to reveal characteristic molecular alterations of SLE, offering new opportunities for disease activity evaluation, therapeutic monitoring, and prognosis prediction.