Functionalized Metal-Organic Frameworks Loaded with Ultra-Small Pt-Se Nanoenzymes Promote Osteoarthritis Repair via...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Orthopedics

Background:

• Osteoarthritis (OA) progression is driven by oxidative stress, hypoxia, and chronic inflammation.
• Nanozymes offer therapeutic potential for OA by mimicking natural enzymes to address these factors.
• Current treatments for OA face limitations in effectively managing the complex pathological microenvironment.

Purpose of the Study:

• To develop and evaluate a novel nano-platform for osteoarthritis (OA) repair.
• To investigate the antioxidant, hypoxia-alleviating, and anti-inflammatory properties of the nano-platform.
• To assess the therapeutic efficacy of the nano-platform in an OA rat model.

Main Methods:

• Fabrication of ultra-small binary hybridized Se-doped Pt nanoparticles (PS NPs) loaded into Zr-based metal-organic frameworks (MOFs) and encapsulated with oxidized chondroitin sulfate (OCS) to form OCS@MOF@PS.
• Evaluation of the multi-enzyme mimetic activities of PS NPs.
• In vitro assessment of OCS@MOF@PS effects on reactive oxygen species (ROS) scavenging, hypoxia alleviation in macrophages, and macrophage polarization (M2 phenotype) via the PI3K/Akt/mTOR pathway.
• In vivo testing of OCS@MOF@PS in an OA rat model, measuring reductions in International Cartilage Repair Society (ICRS) and Mankin scores.

Main Results:

• The OCS@MOF@PS nano-platform demonstrated significant ROS scavenging and hypoxia alleviation in macrophages.
• Macrophage polarization towards the M2 phenotype was induced, potentially mediated by the PI3K/Akt/mTOR pathway.
• In the OA rat model, OCS@MOF@PS treatment resulted in substantial reductions in OA joint damage, with ICRS and Mankin scores decreasing by 78.25 ± 0.28% and 75.70 ± 0.55%, respectively, at 56 days post-treatment.

Conclusions:

• The OCS@MOF@PS nano-platform exhibits potent ROS scavenging and hypoxia-alleviating capabilities.
• This nano-platform demonstrates excellent biocompatibility and significant therapeutic efficacy in an OA rat model.
• OCS@MOF@PS represents a promising therapeutic strategy for osteoarthritis and other inflammatory conditions associated with oxidative stress.