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This work expands the nucleic acid targets for depression from neurons to microglia and uses peptide-guided nanoparticles for intranasal brain delivery, bypassing the blood-brain barrier. In the future, other stress-related circRNAs can be screened to construct multi-target intervention combinations. The targeting strategy of the MG1 peptide can be adapted to delivery needs under different neuroinflammatory conditions. Intranasal administration is suitable for chronic psychiatric disorders requiring long-term, repeated dosing, as it has higher patient compliance. The downstream regulatory network of circMBNL1 and its expression differences in various depression subtypes still need in-depth analysis, but this strategy provides a translatable delivery framework for nucleic acid therapy in psychiatric disorders.
Reference:
DOI:10.1186/s12951-026-04734-2
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