A modular protein-nucleic acid nanodevice for non-genetic engineering of mesenchymal stem cells to target pathological collagen in liver fibrosis

), and the aptamer-based DNA nanostructure was extended from monovalent to multivalent through hybridization chain reaction. The optimized nanodevice rapidly binds to MSCs after 30 min incubation under physiological conditions, which not only preserved stemness and full differentiation potential of MSCs, but also installed a collagen-targeting code, indicating a good biocompatibility and the dual-targeting efficiency of the nanodevice. In a mouse model of carbon tetrachloride-induced liver fibrosis, with one-time intravenous injection, these engineered MSCs exhibited 1.93-fold higher liver retention than the native MSCs, > 90% collagen reduction, and largely restored liver function in 7 days. This study established a multifunctional, programmable targeted cell delivery platform using a plug-and-play cell-surface coding strategy, achieving efficient targeted delivery and preliminarily validating its significant therapeutic effect in a mouse model of liver fibrosis. Considering the modularity of the chimera, this strategy possesses good versatility and can be extended to the targeted therapy of various diseases characterized by pathological collagen deposition, potentially becoming a universal cell functionalization method.