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Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
Published on: June 2, 2023
Therapeutic framework nucleic acid complexes targeting oxidative stress and pyroptosis for the treatment of
Jiafeng Li1, Yifan Li1, Xiushuai Shang1
1Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, China.
Abstract:
Osteoarthritis (OA) is one of the most prevalent joint diseases and severely affects the quality of life in the elderly population. However, there are currently no effective prevention or treatment options for OA. Oxidative stress and pyroptosis play significant roles in the development and progression of OA. To address this issue, we have developed a novel therapeutic approach for OA that targets oxidative stress and pyroptosis. We synthesized tetrahedral framework nucleic acid (tFNAs) to form framework nucleic acid complexes (TNCs), which facilitate the delivery of the naturally occurring polymethoxyflavonoid nobiletin (Nob) to chondrocytes. TNC has demonstrated favorable bioavailability, stability, and biosafety for delivering Nob. Both in vitro and in vivo experiments have shown that TNC can alleviate OA and protect articular cartilage from damage by eliminating oxidative stress, inhibiting pyroptosis, and restoring the extracellular matrix anabolic metabolism of chondrocytes. These findings suggest that TNC has significant potential in the treatment of OA and cartilage injury.
Insights
This study introduces a new treatment for osteoarthritis (OA) using nobiletin delivered by tetrahedral framework nucleic acid complexes (TNCs). TNCs effectively reduce oxidative stress and pyroptosis, protecting cartilage and alleviating OA symptoms.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Orthopedics
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease with no effective treatments.
- Oxidative stress and pyroptosis are key contributors to OA pathogenesis.
- Current therapeutic strategies for OA are limited.
Purpose of the Study:
- To develop a novel therapeutic approach for OA targeting oxidative stress and pyroptosis.
- To evaluate the efficacy of nobiletin delivered by tetrahedral framework nucleic acid complexes (TNCs) for OA treatment.
Main Methods:
- Synthesis of tetrahedral framework nucleic acid (tFNAs) to form TNCs for nobiletin (Nob) delivery.
- In vitro and in vivo studies to assess TNC's bioavailability, stability, biosafety, and therapeutic effects.
- Analysis of chondrocyte oxidative stress, pyroptosis, and extracellular matrix metabolism.
Main Results:
- TNC demonstrated favorable bioavailability, stability, and biosafety for nobiletin delivery.
- TNC treatment significantly alleviated OA symptoms and protected articular cartilage in vitro and in vivo.
- TNC effectively eliminated oxidative stress, inhibited pyroptosis, and restored chondrocyte anabolic metabolism.
Conclusions:
- TNC represents a promising therapeutic strategy for osteoarthritis by targeting oxidative stress and pyroptosis.
- This novel approach holds potential for treating OA and cartilage injury.
- Further research into TNC-mediated drug delivery for joint diseases is warranted.
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