ArticleMaterials today. Bio2026
AT-RvD1 liposomes effectively accumulate in spinal cord and reprogram microglia via ANGPTL4-SUCLG1-propionate axis for treating neuropathic pain.
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
Neuropathic pain (NP) remains a major clinical challenge as current medications are ineffective in treating the underlying cause, and the clinical use of these drugs also has adverse reactions such as addiction. Therefore, specialized pro-resolving mediators (SPMs) may represent a promising therapeutic strategy. Microglia-mediated neuroinflammation is central to NP pathogenesis, yet feasible strategies for precise modulation of microglial inflammatory responses remain limited. Here, we reveal that aspirin-triggered resolvin D1 (AT-RvD1) promotes a shift of microglia toward an anti-inflammatory and pro-repair state via a novel ANGPTL4-SUCLG1-propionate axis, consequently attenuating neuroinflammation and pain hypersensitivity in mice models with NP. To address invasive nature of intrathecal injection limitation in NP clinical treatment, an MG1 peptide-modified liposomal delivery system encapsulating AT-RvD1 (AT-RvD1@Lipo-MG1) is developed. Intravenous administration of this nanoplatform enables effective and targeted delivery of AT-RvD1 to spinal microglia, with robust analgesic and anti-inflammatory effects and favorable biosafety in vivo. This study elucidates a novel mechanism through which AT-RvD1 modulates microglial inflammatory responses and proposes a highly translatable nanotherapeutic strategy for the treatment of NP.
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