ROS-Sensitive MgOSiO2 Nano Capsules for Effective Against Osteoarthritis in Rat Model.

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.