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Functionalized Metal-Organic Frameworks Loaded with Ultra-Small Pt-Se Nanoenzymes Promote Osteoarthritis Repair via Efficient ROS Scavenging and Macrophage Polarization Modulation

Guo, Jiang; Du, Haocheng; Xu, Yue; Cheng, Rui; Liu, Chaozong; Di-Silvio, Lucy; Xia, Zhidao; ... Zhang, Xintao; + view all (2026) Functionalized Metal-Organic Frameworks Loaded with Ultra-Small Pt-Se Nanoenzymes Promote Osteoarthritis Repair via Efficient ROS Scavenging and Macrophage Polarization Modulation. Advanced Healthcare Materials , Article e04802. 10.1002/adhm.202504802. (In press). Green open access

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Abstract

Oxidative stress, hypoxia, and chronic inflammation are key factors driving the progression of osteoarthritis (OA). Nanozymes, which exhibit catalytic activity similar to natural enzymes, is able to promote OA repair through antioxidant, hypoxia alleviation, and regulation of the inflammatory microenvironment, demonstrating significant application potential in OA treatment. In this study, ultra-small binary hybridized Se-doped Pt nanoparticles (PS NPs) are loaded into Zr-based metal-organic frameworks (MOFs) and further encapsulated with oxidized chondroitin sulfate (OCS), ultimately yielding a novel nano-platform (OCS@MOF@PS) for effective OA repair. Due to the bimetallic synergistic catalytic effect, PS NPs exhibited multi-enzyme mimetic activities. In vitro and in vivo studies have demonstrated that OCS@MOF@PS effectively scavenged intracellular ROS, alleviated hypoxia in macrophages, and induced their polarization toward the M2 phenotype. This effect may be associated with the regulation of the PI3K/Akt/mTOR signaling pathway. In OA rat model, OCS@MOF@PS significantly attenuated OA joint damage, achieving 78.25 ± 0.28% and 75.70 ± 0.55% reductions in international cartilage repair society (ICRS) score and Mankin score, respectively, at day 56 post-treatment. In conclusion, this nano-platform, with efficient ROS scavenging activity, hypoxia-alleviating capability and excellent biocompatibility, represents a promising therapeutic strategy for OA and other inflammatory diseases fueled by oxidative stress.

Type: Article
Title: Functionalized Metal-Organic Frameworks Loaded with Ultra-Small Pt-Se Nanoenzymes Promote Osteoarthritis Repair via Efficient ROS Scavenging and Macrophage Polarization Modulation
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/adhm.202504802
Publisher version: https://doi.org/10.1002/adhm.202504802
Language: English
Additional information: This version is the author accepted manuscript. It has been made open access under the Creative Commons (CC BY) licence under the terms of the UCL Intellectual Property (IP) Policy and UCL Publications Policy.
Keywords: Heterogeneous catalysis, hypoxia alleviation, macrophage reprogramming, osteoarthritis, reactive oxygen species scavenging
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Ortho and MSK Science
URI: https://discovery.ucl.ac.uk/id/eprint/10221871
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