ArticleMaterials today. Bio2026
An inflammation-targeted lipid nanoparticle inhibiting ferroptosis for spinal cord injury repair.
Article in Materials today. Bio, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Erythropoietin (EPO) has been considered as a potentially effective drug candidate for the treatment of spinal cord injury (SCI). However, due to insufficient drug accumulation in the lesion site and systemic off-target effects, the clinical translation of EPO is limited. To overcome these limitations, we rationally designed a mannose-modified lipid nanoparticle (MLNP) system as a bioresponsive nanocarrier for targeted delivery of EPO mRNA to CD206-enriched inflammatory macrophages/microglia within the injured spinal cord. The engineered EPO@MLNPs exhibited well-defined physicochemical properties, high mRNA encapsulation efficiency, and enhanced stability, enabling preferential accumulation at the SCI lesion and sustained local translation of therapeutic EPO protein. In a mouse model of SCI, this materials-enabled delivery strategy effectively attenuated neuroinflammation, reduced neuronal loss, preserved serotonergic axonal integrity, and markedly improved motor functional recovery. Mechanistically, integrated transcriptomic profiling and experimental validation demonstrated that EPO@MLNP treatment suppressed ferroptosis by regulating iron metabolism and lipid peroxidation pathways. Overall, this study presents a targeted mRNA nanotherapeutic strategy that modulates both inflammatory and ferroptotic pathways, providing a promising approach for SCI treatment and other neuroinflammatory disorders.
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