Melittin directly binds NRP-1 (a TGF-β co-receptor) to selectively suppress endothelial-to-mesenchymal transition, attenuating pulmonary fibrosis in mice with improved survival at lower doses using nanoparticle delivery.
Co-receptor precisionInstead of blocking TGF-β broadly (causing side effects), melittin targets only NRP-1 — the co-receptor directing TGF-β to fibrosis-driving endothelial cells
What the researchers found
Melittin binds NRP-1 directly (confirmed by docking and SPR), selectively suppresses EndMT via TGF-β/Smad and MAPK inhibition, dose-dependently reduces bleomycin PF and improves survival. M-pLNPs sustain lung levels >24h enabling lower dosing.
Why it matters
Pulmonary fibrosis has limited treatments. Melittin's co-receptor targeting strategy avoids the side effects of broad TGF-β blockade while effectively reducing fibrosis.
How the study worked
Molecular docking, SPR binding, in vitro EndMT assays in high-NRP-1 endothelial cells, bleomycin PF mouse model with dose-response, survival analysis, and M-pLNP in vivo imaging.
What this study cannot tell us
Bleomycin PF model may not replicate human IPF fully. Melittin has known toxicity concerns. M-pLNP manufacturing not scaled.
How to read the evidence
Comprehensive preclinical study with binding confirmation, mechanistic elucidation, in vivo efficacy, and nanoparticle delivery optimization.
When this study was published
Published in 2025.
The bigger picture
Co-receptor targeting with peptides is a precision strategy: instead of blocking a pleiotropic pathway broadly, target the co-receptor that directs it to the pathological cell type.
Questions still open
- Could melittin-NRP-1 targeting be applied to other fibrotic diseases (liver, kidney)?
- How does the nanoparticle formulation affect melittin's known toxicity?
- Would NRP-1-targeting peptides other than melittin be equally effective?
Common questions
How does bee venom treat lung fibrosis?
Is bee venom safe for lungs?
Read the original research
Modulation of endothelial-to-mesenchymal transition via NRP-1 targeting with melittin attenuates pulmonary fibrosis.
Materials today. Bio, 36, 102659
Citation
Hu, Ming; Wan, Yingying; Chen, Jiakang; Zhang, Chengwei; Li, Shuze; Shan, Bingbing; Wu, Ling; Yu, Xiang. (2026). Modulation of endothelial-to-mesenchymal transition via NRP-1 targeting with melittin attenuates pulmonary fibrosis.. Materials today. Bio, 36, 102659. https://doi.org/10.1016/j.mtbio.2025.102659