Fig. 1.

Construction of ROS-responsive nanoparticles and the mechanism of repairing spinal cord injury. (a) ROS Nano@Feb-1 was prepared using mPEG-b-Lys-BECI-TCO as a nanocarrier. Tz-A6 peptide binds to CD44 on the surface of Huc-MSCs and then connects with ROS Nano@Feb-1 via click chemistry thereby enabling cellular drug–carrying. The ROS-induced reaction prompts the cleavage of the mPEG-b-Lys-BECI-TCO hydrophobic boronic acid ester, leading to the formation of hydrophilic residues followed by the release of the drug. At first, Feb-1 was administered intraperitoneal injections immediately after SCI for 7 consecutive days. Then the Huc-MSCs which carry NPs via Tz-A6 peptide were injected into the center of the injury using a microinjector on the seventh day after SCI. The Feb-1 reduced ferroptosis after SCI by promoting xCT and GPX4 expression. The treatment combination of Feb-1, Huc-MSCs, and NPs produces beneficial therapeutic effects, promoting SCI repair.