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Genetically engineered chondrocyte-mimetic nanoplatform attenuates osteoarthritis by blocking IL-1β and restoring
Caifeng Deng1,2,3, Liukang Yu1,2,3, Xuan Zhao1,2,3
1Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Osteoarthritis (OA) is a multifactorial disease characterized by joint inflammation and cartilage degeneration, with no disease-modifying drugs available. The vicious cycle between the inflammatory microenvironment (inflamed soil) and dysfunctional chondrocytes (degeneration-related seeds) drives the chronic progressive deterioration of OA. Here, we report a genetically engineered chondrocyte-mimetic nanoplatform (termed HKL-GECM@MPNPs) comprising a honokiol (HKL)-loaded mitochondrion-targeting nanoparticle core coated with an interleukin-1 receptor type 2 (IL-1R2)-overexpressing chondrocyte membrane. HKL-GECM@MPNPs fuse with OA chondrocytes, transferring IL-1R2 onto the plasma membrane and reprogramming the inflamed microenvironment through IL-1β blockade. Mitochondrion-targeting cores then directly deliver HKL to restore mitochondrial sirtuin-3 in OA chondrocytes, reprogramming the cells' pathological phenotype. Intra-articular injection of HKL-GECM@MPNPs in OA mice reduces inflammation, alleviates joint pain, and mitigates cartilage damage through a synergistic effect. Moreover, HKL-GECM@MPNPs effectively reverse cartilage degeneration in human OA cartilage explants. This approach highlights the potential of HKL-GECM@MPNPs to combine IL-1β blockade and mitochondrial sirtuin-3 restoration as a promising strategy for OA treatment.
Insights
This study introduces a novel nanoplatform for osteoarthritis treatment. It targets inflammation and cartilage degeneration by blocking IL-1β and restoring mitochondrial function, offering a promising therapeutic strategy.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Regenerative Medicine
Background:
- Osteoarthritis (OA) is a degenerative joint disease with no disease-modifying treatments.
- The progression of OA involves joint inflammation and cartilage breakdown.
- Current treatments lack the ability to halt or reverse OA progression.
Purpose of the Study:
- To develop a novel nanoplatform for osteoarthritis treatment.
- To combine anti-inflammatory and chondroprotective effects in a single therapeutic agent.
- To investigate the efficacy of a chondrocyte-mimetic nanoplatform in preclinical OA models.
Main Methods:
- A genetically engineered nanoplatform (HKL-GECM@MPNPs) was created, mimicking chondrocytes.
- The nanoplatform features a honokiol (HKL)-loaded core and an IL-1R2-overexpressing chondrocyte membrane.
- HKL-GECM@MPNPs were tested in OA mouse models and human OA cartilage explants.
Main Results:
- The nanoplatform effectively fused with OA chondrocytes, delivering IL-1R2 and blocking IL-1β.
- Intra-articular injection reduced inflammation, joint pain, and cartilage damage in OA mice.
- Significant reversal of cartilage degeneration was observed in human OA cartilage explants.
Conclusions:
- HKL-GECM@MPNPs demonstrate a synergistic therapeutic effect for osteoarthritis.
- The nanoplatform combines IL-1β blockade with mitochondrial sirtuin-3 restoration.
- This approach presents a promising strategy for developing disease-modifying osteoarthritis treatments.
