Enhancing stem cell therapy efficacy with functional lignin modified cerium-iron nanozyme through magnetic resonance imaging tracking and apoptosis protection in inflammatory environment

Stem cell transplantation provides a promising approach for addressing inflammation and functional disorders. Nonetheless, the viability of these transplanted cells diminishes significantly within pathological environments, limiting their therapeutic potential. Moreover, the non-invasive tracking of these cells in vivo remains a considerable challenge, hampering the assessment of their therapeutic efficacy. Transition-metal oxide nanocrystals, known for their unique “enzyme-like” catalytic property and imaging capability, provide a new avenue for clinical application. In this study, the lignin as a biocompatible macromolecule was modified with poly (ethylene glycol) through chain-transfer polymerization, and then it was utilized to incorporate superparamagnetic iron oxide and cerium oxide nanocrystals creating a functional nanozyme. The iron oxide nanocrystals self-assembled into the hydrophobic core of nano system, while the in-situ mineralization of cerium oxide particles was carried out with the assistance of peripheral phenolic hydroxyl groups. The product, cerium‑iron core-shell nanozyme, enabled effective stem cells labeling through endocytosis and exhibited catalase and superoxide dismutase activities within the cells. As a result, it could scavenge highly destructive hydroxyl radicals and peroxyl radicals, shielding stem cells from apoptosis in inflammatory environment and maintaining their differentiation ability. Additionally, when these functionalized stem cells were administered to mice with acute inflammation, not only did they alleviate disease symptoms, but they also allowed for the visualization using T₂-weighted magnetic resonance imaging. This innovative therapeutic approach provides a new strategy for combatting diseases.