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Updated: Jun 1, 2025
Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
Published on: June 2, 2023
High-Throughput Screening Strategy and Metal-Organic Framework-Based Multifunctional Controlled-Release Nanomaterial
Yu Chen1,2,3, Yekai Zhang1,2,3, Chenyu Wu1,2,3
1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Abstract:
Osteoarthritis (OA) is a prevalent degenerative disease that lacks effective therapy. Oxidative stress is one of the major factors contributing to OA; however, treatments targeting oxidative stress are still lacking. In the current study, we established an oxidative stress-induced cell death model in chondrocytes in vitro and screened drugs that may suppress oxidative stress-induced cell death. Ethyl gallate (EG) was identified as the most potent drug against oxidative stress-induced cell death out of more than 600 drugs in the natural product library. Application of drugs without an appropriate delivery system for OA therapy may have drawbacks such as low bioavailability, short action time, and poor efficacy. Herein, poly-His6-zinc assembly (PZA), a pH-responsive metal-organic framework (MOF) loaded with EG (EG@PZA) was designed for OA therapy. It was demonstrated that EG@PZA may have the lysosome escape property, which dramatically increases the utilization of EG. Furthermore, EG@PZA showed enhanced release capability of EG in the acidic microenvironment. In vitro and in vivo studies demonstrated that EG@PZA effectively suppresses oxidative stress-induced extracellular matrix degradation, ferroptosis, and senescence in chondrocytes and also ameliorates OA in the destabilization of the medial meniscus (DMM) mouse model in vivo. Together, the current study showed that EG@PZA may become a potential controlled-release nanomaterial for effective OA therapy.
Insights
Ethyl gallate (EG) delivered via a pH-responsive nanomaterial (poly-His6-zinc assembly, PZA) effectively treats osteoarthritis by reducing oxidative stress and cell damage. This novel EG@PZA system enhances drug delivery and efficacy for osteoarthritis therapy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) is a widespread degenerative joint disease with limited therapeutic options.
- Oxidative stress significantly contributes to OA pathogenesis, but targeted treatments are scarce.
- Effective OA therapy requires overcoming drug delivery challenges like low bioavailability and short action time.
Purpose of the Study:
- To identify potent natural compounds that combat oxidative stress-induced chondrocyte death.
- To develop an advanced drug delivery system for enhanced osteoarthritis treatment.
- To evaluate the efficacy of a novel nanomaterial loaded with ethyl gallate for OA therapy.
Main Methods:
- Screened over 600 natural products to identify compounds inhibiting oxidative stress-induced chondrocyte death.
- Designed and synthesized poly-His6-zinc assembly (PZA), a pH-responsive metal-organic framework, loaded with ethyl gallate (EG) to create EG@PZA.
- Conducted in vitro and in vivo studies using chondrocytes and a destabilization of the medial meniscus (DMM) mouse model to assess therapeutic effects.
Main Results:
- Ethyl gallate (EG) was identified as a potent inhibitor of oxidative stress-induced chondrocyte death.
- EG@PZA demonstrated lysosome escape properties and enhanced EG release in acidic environments, improving drug utilization.
- EG@PZA effectively suppressed oxidative stress, extracellular matrix degradation, ferroptosis, and senescence in chondrocytes, and ameliorated OA in vivo.
Conclusions:
- EG@PZA represents a promising pH-responsive nanomaterial for targeted osteoarthritis therapy.
- The developed system overcomes limitations of traditional drug delivery, enhancing therapeutic efficacy.
- EG@PZA shows significant potential for future clinical applications in managing osteoarthritis.
