Isoquercitrin-loaded adipose-derived stem cell exosomes synchronize immunomodulation and neurovascular remodeling to accelerate spinal cord regeneration.

Spinal cord injury (SCI) involves complex and interconnected pathological processes, including microglia-driven inflammation, vascular disruption, and impaired neuronal metabolic homeostasis, which collectively limit functional recovery. Here, we developed an isoquercitrin-loaded adipose-derived stem cell exosomes formulation (IQC@ADSCs-EXOs) as a natural nanocarrier delivery platform to coordinately modulate key cellular components within the lesion niche. IQC@ADSCs-EXOs exhibited typical vesicular morphology with nanoscale size distribution and a negative surface potential, and were efficiently internalized by microglia, endothelial cells (ECs), and neurons. Functionally, IQC@ADSCs-EXOs attenuated myelin debris-induced lipid droplet accumulation, lipid peroxidation, and intracellular ROS in BV2 cells, accompanied by a shift toward an anti-inflammatory phenotype. Meanwhile, IQC@ADSCs-EXOs promoted endothelial proliferation, migration, and tube formation, and enhanced mitochondrial activity with increased neurite outgrowth in PC12 cells. In a mouse contusive SCI model, local administration of IQC@ADSCs-EXOs was associated with improved vascular rebuilding, reduced neuroinflammation, enhanced axonal regeneration, and better locomotor and electrophysiological outcomes compared with controls. Collectively, these findings support IQC@ADSCs-EXOs as a nanotherapeutic platform with multicellular targeting capacity and translational potential for SCI repair.