A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression
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 lar...
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2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-03046-7 |
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| author | Qiuyang Wang Kai Feng Guangsheng Wan Wei Liao Jing Jin Peng Wang Xiaolian Sun Weijun Wang Qing Jiang |
| author_facet | Qiuyang Wang Kai Feng Guangsheng Wan Wei Liao Jing Jin Peng Wang Xiaolian Sun Weijun Wang Qing Jiang |
| author_sort | Qiuyang Wang |
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| description | 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. Graphical Abstract |
| format | Article |
| id | doaj-art-b863f9ab20b34712a28ef60fc9cdcbef |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Journal of Nanobiotechnology |
| spelling | doaj-art-b863f9ab20b34712a28ef60fc9cdcbef2025-01-19T12:37:49ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112110.1186/s12951-024-03046-7A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progressionQiuyang Wang0Kai Feng1Guangsheng Wan2Wei Liao3Jing Jin4Peng Wang5Xiaolian Sun6Weijun Wang7Qing Jiang8State 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 SchoolState Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, School of Pharmacy, China Pharmaceutical UniversityState Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, School of Pharmacy, China Pharmaceutical UniversityChildren’s Hospital of Nanjing Medical UniversityState 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 SchoolState 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 SchoolState Key Laboratory of Natural Medicines, Key Laboratory of Drug Quality Control and Pharmacovigilance, School of Pharmacy, China Pharmaceutical UniversityState 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 SchoolState 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 SchoolAbstract 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. Graphical Abstracthttps://doi.org/10.1186/s12951-024-03046-7OsteoarthritisMetalloproteinase-13 siRNA nanocarrierROS-responsive Hydrogel |
| spellingShingle | Qiuyang Wang Kai Feng Guangsheng Wan Wei Liao Jing Jin Peng Wang Xiaolian Sun Weijun Wang Qing Jiang A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression Journal of Nanobiotechnology Osteoarthritis Metalloproteinase-13 siRNA nanocarrier ROS-responsive Hydrogel |
| title | A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression |
| title_full | A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression |
| title_fullStr | A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression |
| title_full_unstemmed | A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression |
| title_short | A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression |
| title_sort | ros responsive hydrogel encapsulated with matrix metalloproteinase 13 sirna nanocarriers to attenuate osteoarthritis progression |
| topic | Osteoarthritis Metalloproteinase-13 siRNA nanocarrier ROS-responsive Hydrogel |
| url | https://doi.org/10.1186/s12951-024-03046-7 |
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