Cabazitaxel Sustained-Release Nanoparticles Treat Spinal Cord Injury through Inhibiting Fibrin Deposition and Improving the Microenvironment

Biomaterial-based modulation of the microenvironment represents a promising neuroprotective strategy for spinal cord injury (SCI). We first fabricated hyaluronic acid (HA)-<i>graft</i>-epigallocatechin gallate (EGCG) nanoparticles (HEN). These nanoparticles can synergistically exert anti-inflammatory and antioxidant effects, while HA can modulate the immune microenvironment. To further enhance therapeutic efficacy, Cabazitaxel (Cab) was incorporated into HEN to generate multifunctional Cabazitaxel-loaded HA-EGCG nanoparticles (Cab-HEN), which inhibited scar formation and modulated microtubule homeostasis, thereby promoting the beneficial regeneration of nerve axons in a rat SCI model. Through in situ injection at the T9 injury site, Cab-HEN significantly downregulated the expression of inflammatory factors, effectively mitigated oxidative damage induced by excessive reactive oxygen species (ROS), and reduced fibrin deposition and scar formation. Furthermore, Cab-HEN regulated microtubules and enhanced the regeneration of nerve fibers. Evaluations based on electrophysiological assessments, Basso, Beattie, and Bresnahan (BBB) scores, and bladder function recovery revealed the nanoparticles' remarkable therapeutic efficacy in SCI. Therefore, biomaterials can facilitate axonal regeneration, tissue remodeling, and functional restoration following injury.