An anti-inflammatory and neuroprotective biomimetic nanoplatform for repairing spinal cord injury

Spinal cord regeneration after a spinal cord injury (SCI) remains a difficult challenge due to the complicated inflammatory microenvironment and neuronal damage at the injury sites. In this study, retinoic acid (RA) and curcumin (Cur) were co-loaded with bovine serum albumin (BSA) self-assembly to obtain RA@BSA@Cur nanoparticles (NPs) for SCI treatment. Cur, as an antioxidant drug, facilitated reactive oxygen species (ROS) scavenging, and decreased the amount of inflammatory factors secreted by macrophages, while RA could enhance neurite extensions and neural differentiation. The constructed RA@BSA@Cur NPs not only induced polarization of macrophages toward pro-regenerative phenotypes and markedly reduced the inflammatory response of macrophages or microglia, but also increased neurite length in PC12 cells and neuronal differentiation of bone marrow mesenchymal stem cells, improved the differentiation of neural stem cells (NSCs) into β3-tubulin+ neurons, and reversed the pro-astrocyte differentiation effect of inflammatory cytokines on NSCs. In vivo experiments revealed that RA@BSA@Cur NPs regulated the phenotypic polarization of macrophages, inhibited the release of inflammatory mediators, promoted functional neuron regeneration and motor function, and further inhibited scar tissue formation. This study highlighted that the BSA-based biomimetic nanomaterials could be used as ROS scavengers and nerve regeneration promoters for treating SCI. [Display omitted] •Retinoic acid and Curcumin with remarkable neuroprotective and antioxidant activities are prepared for spinal cord injury.•RA@BSA@Cur NPs induce polarization of macrophages, reduce levels of tumor necrosis factor-α and interleukin-6, and thus reduce the inflammatory response.•RA@BSA@Cur NPs increase neurite length in PC12 cells and neuronal differentiation of bone marrow mesenchymal stem cells, and regulate the neurons/astrocytes differentiation of NSCs.•RA@BSA@Cur NPs reverse the pro-astrocyte differentiation effect of macrophages-derived inflammatory cytokines on NSCs.•RA@BSA@Cur NPs promote neuron regeneration and motor function, inhibit scar tissue formation, and regulate the phenotypic polarization of macrophages. The BMSCs Differentiation with RA@BSA@Cur NPs: Mice BMSCs were supplied by Wuhan Procell Life Science & Technology Co.,Ltd. The cells (2.0 × 104 cells/mL) were cultured in 24-well plate with DMEM medium (low glucose) containing 10% FBS, treated with different BSA nanoparticles for 7 day