Targeted Repair of Spinal Cord Injury Based on miRNA‐124‐3p–Loaded Mesoporous Silica Camouflaged by Stem Cell Membrane Modified with Rabies Virus Glycoprotein

Abstract

Spinal cord injury (SCI) has no effective treatment modalities. It faces a significant global therapeutical challenge, given its features of poor axon regeneration, progressive local inflammation, and inefficient systemic drug delivery due to the blood–spinal cord barrier (BSCB). To address these challenges, a new nano complex that achieves targeted drug delivery to the damaged spinal cord is proposed, which contains a mesoporous silica nanoparticle core loaded with microRNA and a cloaking layer of human umbilical cord mesenchymal stem cell membrane modified with rabies virus glycoprotein (RVG). The nano complex more readily crosses the damaged BSCB with its exosome‐resembling properties, including appropriate size and a low‐immunogenic cell membrane disguise and accumulates in the injury center because of RVG, where it releases abundant microRNAs to elicit axon sprouting and rehabilitate the inflammatory microenvironment. Culturing with nano complexes promotes axonal growth in neurons and M2 polarization in microglia. Furthermore, it showed that SCI mice treated with this nano complex by tail vein injection display significant improvement in axon regrowth, microenvironment regulation, and functional restoration. The efficacy and biocompatibility of the targeted delivery of microRNA by nano complexes demonstrate their immense potential as a noninvasive treatment for SCI.

The therapeutic potential of microRNAs to ameliorate spinal cord injury by regulating oligodendrocyte progenitor cells and remyelination

“…On the other hand, biomaterial-based engineered nanoparticles can also cross the blood–brain barrier, realize target delivery of miRNAs to certain organs and cells, and sustain the release of miRNAs ( Lee et al, 2019 ). miR-124-3p-loaded nanoparticles coated by a modified stem cell membrane could cross the damaged BSCB, accumulate in the lesion area, and release sufficient miRNAs to modulate the local microenvironment and promote axon outgrowth after SCI ( Fan et al, 2024 ). In addition, nanoparticles can be modified with certain peptides or antibodies to target specific cells in the lesion microenvironment.…”