Carrier-Free Nanodrug Based on Co-Assembly of Methylprednisolone Dimer and Rutin for Combined Treatment of Spinal Cord Injury

Spinal cord injury (SCI), which is characterized by excessiveinflammatorycell infiltration and accumulation of oxidative substance, would severelyimpede neurological functional recovery and lead to permanent andprofound neurologic deficits and even disability. Methylprednisolone(MP) is the most commonly used clinical anti-inflammatory drug forSCI treatment, but high doses are typically required that can causesevere side effects. Here, we developed a carrier-free thioketal linkedMP dimer@rutin nanoparticles (MP2-TK@RU NPs) which canachieve combined SCI treatment by coassembling reactive oxygen species(ROS) cleavable MP dimers and rutin. This proposed nanodrug possessesthe following favorable advantages: (1) the carrier-free system iseasily accessible and has a high drug-loading capacity, which is preferredby the pharmaceutical industry; (2) The ROS-cleavable linker increasesthe efficiency of targeted drug delivery to the injury site; (3) Rutin,a type of plant-derived natural flavonoid with good biocompatibility,anti-inflammatory, and antioxidant properties, is codelivered to enhancethe therapy outcomes. The obtained MP2-TK@RU NPs exhibitedpotent anti-inflammatory and antioxidative properties both in vitro and in vivo, demonstrating superiorlocomotor function recovery and neuroprotective efficacy in rats withSCI. This carrier-free nanodrug is anticipated to provide a promisingtherapeutic strategy for clinical SCI treatment.