Spinal cord injury (SCI) treatment requires a nanosystem for drug delivery that can effectively penetrate the blood-spinal cord barrier (BSCB). Herein, we designed poly(2-methacryloyloxyethyl phosphorylgallylcholine) (PMPC)/l-arginine (PMPC/A)-based nanomotors that can release nitric oxide (NO). The nanomotors were loaded with the inducible NO synthase inhibitor 1400W and nerve growth factor (NGF). PMPC with a zwitterionic structure not only provided good biocompatibility for the nanomotors but also facilitated their passage through the BSCB owing to the assistance of a large number of choline transporters on the BSCB. Additionally, the l-arginine loaded on the nanomotors was able to react with reactive oxygen species in the microenvironment of the injured nerve to produce NO, thereby conferring the ability of autonomic movement to the nanomotors, which facilitated the uptake of drugs by cells in damaged areas and penetration in pathological tissues. Moreover, in vivo animal experiments indicated that the PMPC/A/1400W/NGF nanomotors could effectively pass through the BSCB and restore the motion function of a rat SCI model by regulating its internal environment as well as the release of therapeutic drugs. Thus, the drug delivery system based on nanomotor technology offers a promising strategy for treating central nervous system diseases.
Keywords: adjust pathological microenvironment; blood−spinal cord barrier; drug-loaded nanomotor; spinal cord injury; zwitterionic structure.