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Updated: Jun 2, 2025
Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
Published on: June 2, 2023
A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate
Qiuyang Wang1,2,3, Kai Feng4, Guangsheng Wan4
1State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, People's Republic of China.
Abstract:
RNA interference (RNAi) and oxidative stress inhibition therapeutic strategies have been extensively utilized in the treatment of osteoarthritis (OA), the most prevalent degenerative joint disease. However, the synergistic effects of these approaches on attenuating OA progression remain largely unexplored. In this study, matrix metalloproteinase-13 siRNA (siMMP-13) was incorporated onto polyethylenimine (PEI)-polyethylene glycol (PEG) modified Fe3O4 nanoparticles, forming a nucleic acid nanocarrier termed si-Fe NPs. Subsequently, a poly(vinyl alcohol) (PVA) crosslinked phenylboronic acid (PBA)-modified hyaluronic acid (HA) hydrogel (HPP) was used to encapsulate the si-Fe NPs, resulting in a bifunctional hydrogel (si-Fe-HPP) with reactive oxygen species (ROS)-responsive and RNAi therapeutic properties. Studies in vitro demonstrated that si-Fe-HPP exhibited excellent biocompatibility, anti-inflammatory effects and prolonged stable retention time in knee joint. Intra-articular injection of si-Fe-HPP significantly attenuated cartilage degradation in mice with destabilization of the medial meniscus (DMM)-induced OA. The si-Fe-HPP treatment not only notably alleviated synovitis, osteophyte formation and subchondral bone sclerosis, but also markedly improved physical activity and reduced pain in DMM-induced OA mice. This study reveals that si-Fe-HPP, with its ROS-responsive and RNAi abilities, can significantly protect chondrocytes and attenuate OA progression, providing novel insights and directions for the development of therapeutic materials for OA treatment.
Insights
This study developed a novel hydrogel (si-Fe-HPP) combining RNA interference and oxidative stress inhibition for osteoarthritis treatment. The treatment effectively reduced cartilage degradation and pain in OA mice.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Regenerative Medicine
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease.
- Current treatments for OA, including RNA interference (RNAi) and oxidative stress inhibition, have limitations.
- The synergistic effects of combined RNAi and oxidative stress inhibition for OA remain underexplored.
Purpose of the Study:
- To develop a novel bifunctional hydrogel (si-Fe-HPP) for osteoarthritis treatment.
- To investigate the synergistic therapeutic effects of RNAi and ROS-responsive properties in OA.
- To evaluate the efficacy of si-Fe-HPP in an in vivo OA model.
Main Methods:
- siRNA targeting matrix metalloproteinase-13 (siMMP-13) was loaded onto Fe3O4 nanoparticles (si-Fe NPs).
- si-Fe NPs were encapsulated within a ROS-responsive hyaluronic acid hydrogel (HPP) to form si-Fe-HPP.
- In vitro biocompatibility and anti-inflammatory effects were assessed.
- Efficacy was evaluated in mice with destabilization of the medial meniscus (DMM)-induced OA via intra-articular injection.
Main Results:
- si-Fe-HPP demonstrated excellent biocompatibility, anti-inflammatory effects, and prolonged retention in the knee joint.
- Intra-articular injection of si-Fe-HPP significantly attenuated cartilage degradation in DMM-induced OA mice.
- The treatment alleviated synovitis, osteophyte formation, subchondral bone sclerosis, improved physical activity, and reduced pain.
Conclusions:
- si-Fe-HPP exhibits significant chondroprotective effects and attenuates OA progression.
- The developed hydrogel provides a promising therapeutic strategy for osteoarthritis by combining RNAi and ROS-responsive properties.
- This study offers novel insights for developing advanced therapeutic materials for OA treatment.
