Antioxidant Nanozyme-Engineered Mesenchymal Stem Cells for in Vivo MRI Tracking and Synergistic Therapy of Myocardial Infarction

Cell therapy is a promising approach for myocardial infarction (MI) treatment. However, this strategy is often restricted by the harsh microenvironment of MI, such as excess ROS, high oxidative stress, inflammation, etc., and thus decreases the curative effect. Additionally, the distribution, migration, and homing of the transplanted stem cells is ambiguous, which also becomes a bottleneck for clinical translation. To address these challenges, herein, a versatile antioxidant nanozyme is designed by polymerically modifying dopamine (PDA) onto the surface of Mn3O4. The obtained nanozyme acts as an efficient SOD mimic, eliminating ROS, relieving oxidative stress, and reducing inflammation to improve the MI microenvironment. Simultaneously, Mn3O4@PDA serves as an excellent MRI contrast agent for tracking MSCs. Then, MSCs are engineered with Mn3O4@PDA nanozyme via endocytosis to form Mn3O4@PDA-MSCs (Abbr. E-MSCs), which possess superior viability, migration and homing ability compared to normal MSCs. Furthermore, E-MSCs exhibit superior anti-oxidant and anti-inflammatory activity, thereby enhancing the therapeutic efficacy of MSCs. Finally, the in vivo MRI tracking and synergistic therapy potential of E-MSCs is explored in MI model mice. Overall, this work provides a strategy to combine antioxidant activity and imaging properties of nanozymes to simultaneously facilitate imaging tracking of stem cells and improve MI treatment. Mn3O4@PDA nanozyme-engineered MSCs exhibit the combination of antioxidant activity and MRI property to simultaneously facilitate imaging tracking of MSCs and enhance MI treatment by improving the microenvironment. image