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Nanodrugs Targeting Key Factors of Ferroptosis Regulation for Enhanced Treatment of Osteoarthritis
https://orcid.org/0000-0001-8795-0874
AbstractOsteoarthritis (OA) is a globally prevalent degenerative joint disease. Recent studies highlight the role of ferroptosis in OA progression. Targeting ferroptosis regulation presents a promising therapeutic strategy for OA; however, current research primarily focuses on single targets associated with ferroptosis. In this study, a reactive oxygen species (ROS)‐responsive nanoparticle is developed by linking deferasirox (DEF) and pterostilbene (PTE) with thioketal and incorporating cerium ions (Ce), creating Ce@D&P nanoparticles (NPs), which offer multitarget regulation of ferroptosis. The characteristics of Ce@D&P NPs are evaluated and their therapeutic effects on IL‐1β‐stimulated chondrocytes are verified. Results show that Ce@D&P NPs reduce ROS levels, mitigate inflammation, chelate iron to inhibit ferroptosis, and balance extracellular matrix (ECM) metabolism in chondrocytes. Mechanistically, transcriptomics and metabolomics analyses suggest that Ce@D&P NPs exerted their effects by regulating oxidative stress and lipid metabolism in chondrocytes. To better treat destabilization of the medial meniscus (DMM)‐induced OA in mice, Ce@D&P NPs via intra‐articular injection are delivered. The results show that Ce@D&P NPs alleviate cartilage matrix damage and slow OA progression. Overall, the findings indicate that Ce@D&P NPs represent a promising multitarget drug delivery system, and Ce@D&P NPs may be an effective strategy for OA treatment.
Nanodrugs Targeting Key Factors of Ferroptosis Regulation for Enhanced Treatment of Osteoarthritis
https://orcid.org/0000-0001-8795-0874
AbstractOsteoarthritis (OA) is a globally prevalent degenerative joint disease. Recent studies highlight the role of ferroptosis in OA progression. Targeting ferroptosis regulation presents a promising therapeutic strategy for OA; however, current research primarily focuses on single targets associated with ferroptosis. In this study, a reactive oxygen species (ROS)‐responsive nanoparticle is developed by linking deferasirox (DEF) and pterostilbene (PTE) with thioketal and incorporating cerium ions (Ce), creating Ce@D&P nanoparticles (NPs), which offer multitarget regulation of ferroptosis. The characteristics of Ce@D&P NPs are evaluated and their therapeutic effects on IL‐1β‐stimulated chondrocytes are verified. Results show that Ce@D&P NPs reduce ROS levels, mitigate inflammation, chelate iron to inhibit ferroptosis, and balance extracellular matrix (ECM) metabolism in chondrocytes. Mechanistically, transcriptomics and metabolomics analyses suggest that Ce@D&P NPs exerted their effects by regulating oxidative stress and lipid metabolism in chondrocytes. To better treat destabilization of the medial meniscus (DMM)‐induced OA in mice, Ce@D&P NPs via intra‐articular injection are delivered. The results show that Ce@D&P NPs alleviate cartilage matrix damage and slow OA progression. Overall, the findings indicate that Ce@D&P NPs represent a promising multitarget drug delivery system, and Ce@D&P NPs may be an effective strategy for OA treatment.
Nanodrugs Targeting Key Factors of Ferroptosis Regulation for Enhanced Treatment of Osteoarthritis
https://orcid.org/0000-0001-8795-0874
AbstractOsteoarthritis (OA) is a globally prevalent degenerative joint disease. Recent studies highlight the role of ferroptosis in OA progression. Targeting ferroptosis regulation presents a promising therapeutic strategy for OA; however, current research primarily focuses on single targets associated with ferroptosis. In this study, a reactive oxygen species (ROS)‐responsive nanoparticle is developed by linking deferasirox (DEF) and pterostilbene (PTE) with thioketal and incorporating cerium ions (Ce), creating Ce@D&P nanoparticles (NPs), which offer multitarget regulation of ferroptosis. The characteristics of Ce@D&P NPs are evaluated and their therapeutic effects on IL‐1β‐stimulated chondrocytes are verified. Results show that Ce@D&P NPs reduce ROS levels, mitigate inflammation, chelate iron to inhibit ferroptosis, and balance extracellular matrix (ECM) metabolism in chondrocytes. Mechanistically, transcriptomics and metabolomics analyses suggest that Ce@D&P NPs exerted their effects by regulating oxidative stress and lipid metabolism in chondrocytes. To better treat destabilization of the medial meniscus (DMM)‐induced OA in mice, Ce@D&P NPs via intra‐articular injection are delivered. The results show that Ce@D&P NPs alleviate cartilage matrix damage and slow OA progression. Overall, the findings indicate that Ce@D&P NPs represent a promising multitarget drug delivery system, and Ce@D&P NPs may be an effective strategy for OA treatment.
Nanodrugs Targeting Key Factors of Ferroptosis Regulation for Enhanced Treatment of Osteoarthritis
Advanced Science
Wang, Dong (author) / Pan, Yanli (author) / Chen, Wenzhe (author) / He, Du (author) / Qi, Weihui (author) / Chen, Jiali (author) / Yuan, Wenhua (author) / Yang, Yimin (author) / Chen, Di (author) / Wang, Pinger (author)
Advanced Science ; 12
2025-03-01
Article (Journal)
Electronic Resource
English
Nanodrugs Targeting Key Factors of Ferroptosis Regulation for Enhanced Treatment of Osteoarthritis
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