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已发表论文
ROS 敏感型 MgOSiO₂ 纳米胶囊在大鼠骨关节炎模型中具有显著疗效
Authors Zheng Y , Zhang Z, Cui Y, Liu N , Ma H, Wang B, Li R, Zhu N, Zhang N
Received 9 June 2025
Accepted for publication 5 September 2025
Published 14 September 2025 Volume 2025:20 Pages 11235—11248
DOI https://doi.org/10.2147/IJN.S536547
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Professor Farooq A. Shiekh
Yu Zheng,1,* Zhouxiaolong Zhang,2,* Yingna Cui,3 Na Liu,1 Hongting Ma,2 Benjie Wang,1 Ruixin Li,1 Nan Zhu,2 Nan Zhang1
1Department of Orthopedics, The Affiliated Xinhua Hospital of Dalian University, Dalian, Liaoning Province, People’s Republic of China; 2School of Chemistry, Dalian University of Technology, Dalian, Liaoning Province, People’s Republic of China; 3School of Chemistry, Dalian University, Dalian, Liaoning Province, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Nan Zhang, Email zhn1979-08@163.com Nan Zhu, Email nanzhu@dlut.edu.cn
Introduction: Magnesium oxide nanoparticles (MgO NPs) as magnesium ionophores have shown potential as a therapeutic strategy for osteoarthritis. However, the rapid absorption and clearance of MgO NPs in the joint cavity and the lack of a clear underlying mechanism may limit their therapeutic efficacy.
Methods: MgO@SiO2 nano capsules were synthesized as a controlled-release nanosystem to mitigate the rapid clearance and potential toxicity of MgO NPs. The physicochemical properties and surface charge of the nano capsules were examined through TEM, EDS, XRD and Zeta potential. The kinetics of nano capsule degradation were measured using using inductively coupled plasma optical emission spectrometry and pH monitoring both in vivo and in vitro. Cytotoxicity and reactive oxygen species (ROS) were monitored to assess the dose-dependent effect of MgO@SiO2 on ROS-mediated oxidative stress. Finally, ROS production and the expression of proinflammatory factors (IL-6, MMP-13, COX-2) were quantified in the cartilage of osteoarthritis samples to evaluate the potential mechanism of action of the nanocapsules for treating osteoarthritis.
Results: MgO@SiO2 nano capsules extended the duration of MgO NPs release from 12 h to 3– 5 days both in vivo and in vitro. MgO@SiO2 exhibited no cytotoxicity toward chondrocytes at formula concentrations < 15 mM. Notably, low concentrations (5 mM) of MgO@SiO2 (and thus of MgO NPs) suppressed ROS generation in chondrocytes, whereas higher concentrations (> 10 mM) increased ROS production. In a rat model of osteoarthritis, intra-articular injection of 5 mM MgO@SiO2 samples significantly alleviated cartilage degeneration and destruction. Finally, ROS levels and the expression of certain proinflammatory factors (IL-6, MMP-13, COX-2)] in articular cartilage were markedly reduced.
Conclusion: As a multi-functional ROS-responsive nanosystem, MgO@SiO2 nano capsules not only slow the release of MgO NPs and reduce their cytotoxicity but also reduce ROS production and thus lessen the inflammatory response in cartilage. This dual-action mechanism achieves therapeutic efficacy for osteoarthritis, offering a promising strategy to delay or reverse osteoarthritis progression.
Keywords: ROS-responsive nanosystem, MgO@SiO2 nanocapsules, antioxidative stress, osteoarthritis
1Department of Orthopedics, The Affiliated Xinhua Hospital of Dalian University, Dalian, Liaoning Province, People’s Republic of China; 2School of Chemistry, Dalian University of Technology, Dalian, Liaoning Province, People’s Republic of China; 3School of Chemistry, Dalian University, Dalian, Liaoning Province, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Nan Zhang, Email zhn1979-08@163.com Nan Zhu, Email nanzhu@dlut.edu.cn
Introduction: Magnesium oxide nanoparticles (MgO NPs) as magnesium ionophores have shown potential as a therapeutic strategy for osteoarthritis. However, the rapid absorption and clearance of MgO NPs in the joint cavity and the lack of a clear underlying mechanism may limit their therapeutic efficacy.
Methods: MgO@SiO2 nano capsules were synthesized as a controlled-release nanosystem to mitigate the rapid clearance and potential toxicity of MgO NPs. The physicochemical properties and surface charge of the nano capsules were examined through TEM, EDS, XRD and Zeta potential. The kinetics of nano capsule degradation were measured using using inductively coupled plasma optical emission spectrometry and pH monitoring both in vivo and in vitro. Cytotoxicity and reactive oxygen species (ROS) were monitored to assess the dose-dependent effect of MgO@SiO2 on ROS-mediated oxidative stress. Finally, ROS production and the expression of proinflammatory factors (IL-6, MMP-13, COX-2) were quantified in the cartilage of osteoarthritis samples to evaluate the potential mechanism of action of the nanocapsules for treating osteoarthritis.
Results: MgO@SiO2 nano capsules extended the duration of MgO NPs release from 12 h to 3– 5 days both in vivo and in vitro. MgO@SiO2 exhibited no cytotoxicity toward chondrocytes at formula concentrations < 15 mM. Notably, low concentrations (5 mM) of MgO@SiO2 (and thus of MgO NPs) suppressed ROS generation in chondrocytes, whereas higher concentrations (> 10 mM) increased ROS production. In a rat model of osteoarthritis, intra-articular injection of 5 mM MgO@SiO2 samples significantly alleviated cartilage degeneration and destruction. Finally, ROS levels and the expression of certain proinflammatory factors (IL-6, MMP-13, COX-2)] in articular cartilage were markedly reduced.
Conclusion: As a multi-functional ROS-responsive nanosystem, MgO@SiO2 nano capsules not only slow the release of MgO NPs and reduce their cytotoxicity but also reduce ROS production and thus lessen the inflammatory response in cartilage. This dual-action mechanism achieves therapeutic efficacy for osteoarthritis, offering a promising strategy to delay or reverse osteoarthritis progression.
Keywords: ROS-responsive nanosystem, MgO@SiO2 nanocapsules, antioxidative stress, osteoarthritis