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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.

Sec. Nanobiotechnology

Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1641236

Anti-Inflammatory Therapy for tendinopathy using Il1rn mRNA encapsulated in SM102 lipid nanoparticles

Provisionally accepted
Yuan ZhangYuan Zhang1,2Xu LiXu Li3Hao LiHao Li4Ruiyang ZhangRuiyang Zhang4Ti ZhangTi Zhang5Talante JumaTalante Juma1Yongfei ZhouYongfei Zhou6Quanyi GuoQuanyi Guo4*Hui ZhaoHui Zhao2*Yongping CaoYongping Cao1*
  • 1Department of Orthopedics, Peking University First Hospital, Beijing, China
  • 2Key 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 China
  • 3National Center for Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
  • 4Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital, Beijing, China
  • 5Department of Orthopedics, Peking University Third Hospital,, Beijing, China
  • 6Institute of Hemu biotechnology, Beijing Hemu Biotechnology Co., Ltd, Beijing, China

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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 hours 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 nonsurgical solution for refractory tendinopathies. Its adaptable design allows expansion to other regenerative targets, advancing precision treatment for musculoskeletal degeneration.

Keywords: Tendinopathy, mRNA therapy, SM102 lipid nanoparticles, Interleukin-1 receptor antagonist, anti-inflammatory therapy

Received: 06 Jun 2025; Accepted: 29 Jul 2025.

Copyright: © 2025 Zhang, Li, Li, Zhang, Zhang, Juma, Zhou, Guo, Zhao and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Quanyi Guo, Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital, Beijing, China
Hui Zhao, Key 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 China
Yongping Cao, Department of Orthopedics, Peking University First Hospital, Beijing, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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