ArticleNature nanotechnology2026
A disease-severity-responsive nanoparticle enables potent ghrelin messenger RNA therapy in osteoarthritis.
Article in Nature nanotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Materialogenetics: an emerging and promising framework for cell-specific genetic manipulation.Bioactive materials · 2026Article
- From oral decoction to intra-articular nanomedicine: Bawei Tiaosui Decoction (BWTSD) nanoparticle-laden lubricating hydrogel for synergistic treatment of knee osteoarthritis.Materials today. Bio · 2026Article
- What's next for osteoarthritis gene therapy?Frontiers in bioengineering and biotechnology · 2026Review
- Target-Specific Extracorporeal Shockwave Therapy Modulates TLR4/NF-κB/MMP13 Signaling Within the Joint Microenvironment to Improve Osteochondral Pathology in Patellofemoral Osteoarthritis.International journal of medical sciences · 2026Article
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Authors and funding
22 authors.
Funding
Abstract
Intra-articular RNA therapeutics have shown promise in osteoarthritis (OA); however, maximizing their efficacy requires targeted delivery to degenerating cartilage within focal lesions. As OA progresses, cartilage degeneration worsens, necessitating disease-responsive targeting with enhanced delivery in advanced stages. Here we develop an anionic nanoparticle (NP) strategy for targeting glycosaminoglycan loss, a hallmark of OA's progression that reduces cartilage's negative charge. These NPs selectively diffuse and accumulate into matrix regions inversely correlated with glycosaminoglycan content owing to reduced electrostatic repulsion, a strategy we term 'matrix inverse targeting' (MINT). In a mouse model of OA, intra-articular delivery of luciferase messenger RNA-loaded MINT NPs demonstrated disease-severity-responsive expression. Using this strategy, we delivered ghrelin mRNA, as ghrelin has shown chondroprotection properties previously. Ghrelin mRNA-loaded MINT NPs reduced cartilage degeneration, subchondral bone thickening and nociceptive pain. Our findings highlight the potential of ghrelin mRNA delivery as a disease-modifying therapy for OA and the platform's potential for lesion-targeted RNA delivery responsive to disease severity.
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Registered trials
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