DNA-Guided Multivalent Antibody Display Boosts the Targeting Performance of Therapeutic Nanovesicles

Nanovesicles (NVs) have recently gained increasing attention in biomedical applications as alternatives to extracellular vesicles. However, their clinical translation is hindered by limited targeting specificity toward diseased tissues. In this study, we present a DNA-mediated self-assembly strategy to construct multivalent antibody-modified nanovesicles (Multi-NVs) for enhanced targeted delivery. Our results demonstrated that Multi-NVs prepared from mesenchymal stromal cells exhibited robust and specific targeting capabilities, improved cellular uptake efficiency, and promoted endothelial angiogenic activity. Importantly, this modular strategy demonstrated broad applicability across multiple disease models, including acute lung injury (ALI) and acute kidney injury, where Multi-NVs achieved markedly improved tissue targeting. Therapeutically, Multi-NV treatment significantly reduced macrophage infiltration and alleviated lung tissue damage and oxidative stress in ALI, highlighting their potential for precision medicine and personalized therapeutic interventions.