Minocycline-Loaded BMSC Exosomes Modulate M1/M2 Macrophage Polarization and Reduce Inflammation after Spinal Cord Injury

Spinal cord injury (SCI) profoundly impacts the central nervous system and significantly affects the lives and health of patients. SCI is characterized by a primary injury and subsequent secondary injury, which includes oxidative stress, inflammation, and apoptosis. Effectively addressing inflammation and apoptosis is crucial for SCI treatment. Minocycline (MnCy), while a widely used anti-inflammatory drug, suffers from limited efficacy in SCI treatments due to its poor targeting capabilities. Our research has identified that folic acid (FA) can improve the targeting of anti-inflammatory agents to macrophages through the activation of folate receptors 1 and 2. Additionally, exosomes derived from bone marrow mesenchymal stem cells (BMSCs) leverage the regenerative properties of stem cells and address the challenge of their low local survival rates. In this study, we engineered FA-modified BMSC-derived exosomes loaded with MnCy (FA-Exo-MnCy). Our in vivo imaging demonstrated that FA-Exo-MnCy specifically accumulates at the injury site, where it exerts a significant anti-inflammatory effect. Pharmacodynamic studies further confirmed that FA-Exo-MnCy effectively reduces both inflammation and apoptosis, showcasing its potential as a promising treatment option for SCI.