Anti-inflammatory therapy for tendinopathy using Il1rn mRNA encapsulated in SM102 lipid nanoparticles
Tendinopathy treatment is hindered by persistent inflammation and irreversible matrix degradation, with current therapies offering transient symptom relief without addressing disease progression. Here, we developed an mRNA-based anti-inflammatory strategy utilizing SM102 lipid nanoparticles (LNPs) t...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1641236/full |
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| author | Yuan Zhang Yuan Zhang Xu Li Hao Li Ruiyang Zhang Ti Zhang Talante Juma Yongfei Zhou Quanyi Guo Hui Zhao Yongping Cao |
| author_facet | Yuan Zhang Yuan Zhang Xu Li Hao Li Ruiyang Zhang Ti Zhang Talante Juma Yongfei Zhou Quanyi Guo Hui Zhao Yongping Cao |
| author_sort | Yuan Zhang |
| collection | DOAJ |
| description | Tendinopathy treatment is hindered by persistent inflammation and irreversible matrix degradation, with current therapies offering transient symptom relief without addressing disease progression. Here, we developed an mRNA-based anti-inflammatory strategy utilizing SM102 lipid nanoparticles (LNPs) to deliver interleukin-1 receptor antagonist (Il1rn) mRNA for tendon repair. SM102-LNPs demonstrated efficient transfection of primary tendon stem cells, sustaining IL-1RA protein expression for over 72 h and neutralizing IL-1β-induced inflammatory cascades. In vitro, IL-1RA suppressed pro-inflammatory cytokines (TNF-α, IL-6, iNOS), restored collagen I/III balance, and enhanced cell migration. In collagenase-induced tendinopathy mice, a single SM102-Il1rn mRNA injection attenuated inflammation, reduced MMP1/13 expression, and improved collagen alignment within 1 week. By 4 weeks, treated tendons exhibited functional recovery with normalized gait patterns. Transcriptomics revealed dual modulation of IL-1 signaling and extracellular matrix (ECM) remodeling pathways, alongside macrophage polarization and oxidative stress regulation. Systemic safety was confirmed by unaltered serum biomarkers and organ histology. This SM102-Il1rn mRNA therapy enables spatiotemporally controlled anti-inflammatory therapy, providing a promising non-surgical solution for refractory tendinopathies. Its adaptable design allows expansion to other regenerative targets, advancing precision treatment for musculoskeletal degeneration. |
| format | Article |
| id | doaj-art-40568a59ab3d453b8a8df379e9ced922 |
| institution | Kabale University |
| issn | 2296-4185 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj-art-40568a59ab3d453b8a8df379e9ced9222025-08-20T03:41:54ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852025-08-011310.3389/fbioe.2025.16412361641236Anti-inflammatory therapy for tendinopathy using Il1rn mRNA encapsulated in SM102 lipid nanoparticlesYuan Zhang0Yuan Zhang1Xu Li2Hao Li3Ruiyang Zhang4Ti Zhang5Talante Juma6Yongfei Zhou7Quanyi Guo8Hui Zhao9Yongping Cao10Department of Orthopedics, Peking University First Hospital, Beijing, ChinaKey Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, ChinaNational Center for Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, ChinaBeijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaBeijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaDepartment of Orthopedics, Peking University Third Hospital, Beijing, ChinaDepartment of Orthopedics, Peking University First Hospital, Beijing, ChinaInstitute of Hemu Biotechnology, Beijing Hemu Biotechnology Co., Ltd., Beijing, ChinaBeijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaKey Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, ChinaDepartment of Orthopedics, Peking University First Hospital, Beijing, ChinaTendinopathy treatment is hindered by persistent inflammation and irreversible matrix degradation, with current therapies offering transient symptom relief without addressing disease progression. Here, we developed an mRNA-based anti-inflammatory strategy utilizing SM102 lipid nanoparticles (LNPs) to deliver interleukin-1 receptor antagonist (Il1rn) mRNA for tendon repair. SM102-LNPs demonstrated efficient transfection of primary tendon stem cells, sustaining IL-1RA protein expression for over 72 h and neutralizing IL-1β-induced inflammatory cascades. In vitro, IL-1RA suppressed pro-inflammatory cytokines (TNF-α, IL-6, iNOS), restored collagen I/III balance, and enhanced cell migration. In collagenase-induced tendinopathy mice, a single SM102-Il1rn mRNA injection attenuated inflammation, reduced MMP1/13 expression, and improved collagen alignment within 1 week. By 4 weeks, treated tendons exhibited functional recovery with normalized gait patterns. Transcriptomics revealed dual modulation of IL-1 signaling and extracellular matrix (ECM) remodeling pathways, alongside macrophage polarization and oxidative stress regulation. Systemic safety was confirmed by unaltered serum biomarkers and organ histology. This SM102-Il1rn mRNA therapy enables spatiotemporally controlled anti-inflammatory therapy, providing a promising non-surgical solution for refractory tendinopathies. Its adaptable design allows expansion to other regenerative targets, advancing precision treatment for musculoskeletal degeneration.https://www.frontiersin.org/articles/10.3389/fbioe.2025.1641236/fulltendinopathymRNA therapySM102 lipid nanoparticlesinterleukin-1 receptor antagonistanti-inflammatory therapy |
| spellingShingle | Yuan Zhang Yuan Zhang Xu Li Hao Li Ruiyang Zhang Ti Zhang Talante Juma Yongfei Zhou Quanyi Guo Hui Zhao Yongping Cao Anti-inflammatory therapy for tendinopathy using Il1rn mRNA encapsulated in SM102 lipid nanoparticles Frontiers in Bioengineering and Biotechnology tendinopathy mRNA therapy SM102 lipid nanoparticles interleukin-1 receptor antagonist anti-inflammatory therapy |
| title | Anti-inflammatory therapy for tendinopathy using Il1rn mRNA encapsulated in SM102 lipid nanoparticles |
| title_full | Anti-inflammatory therapy for tendinopathy using Il1rn mRNA encapsulated in SM102 lipid nanoparticles |
| title_fullStr | Anti-inflammatory therapy for tendinopathy using Il1rn mRNA encapsulated in SM102 lipid nanoparticles |
| title_full_unstemmed | Anti-inflammatory therapy for tendinopathy using Il1rn mRNA encapsulated in SM102 lipid nanoparticles |
| title_short | Anti-inflammatory therapy for tendinopathy using Il1rn mRNA encapsulated in SM102 lipid nanoparticles |
| title_sort | anti inflammatory therapy for tendinopathy using il1rn mrna encapsulated in sm102 lipid nanoparticles |
| topic | tendinopathy mRNA therapy SM102 lipid nanoparticles interleukin-1 receptor antagonist anti-inflammatory therapy |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2025.1641236/full |
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