Dextran sulfate-triamcinolone acetonide conjugate nanoparticles for targeted treatment of osteoarthritis
Autor: | Shujun Dong, Shuai Bian, Yuanqiang Cheng, Jianguo Liu, Chunsheng Xiao, Wanguo Liu, Peng She |
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Rok vydání: | 2020 |
Předmět: |
Triamcinolone acetonide
medicine.drug_class 02 engineering and technology Osteoarthritis Biochemistry Flow cytometry Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound Structural Biology medicine Scavenger receptor Molecular Biology 030304 developmental biology 0303 health sciences medicine.diagnostic_test Cartilage General Medicine 021001 nanoscience & nanotechnology medicine.disease medicine.anatomical_structure Dextran chemistry Cancer research Corticosteroid 0210 nano-technology medicine.drug |
Zdroj: | International Journal of Biological Macromolecules. 158:1082-1089 |
ISSN: | 0141-8130 |
DOI: | 10.1016/j.ijbiomac.2020.05.013 |
Popis: | Osteoarthritis (OA) is a synovial inflammatory condition characterized by cartilage destruction and osteophyte formation. Macrophages play a central role in OA pathogenesis by producing proinflammatory cytokines. Intra-articular corticosteroid administration can relieve refractory pain and inflamed effusion of knee joints. However, limitations, such as rapid clearance from the joint space, potential damage to articular cartilage, and accelerated joint degeneration, may hamper the clinical application of corticosteroids. In this study, we reported the design and preparation of dextran sulfate-triamcinolone acetonide conjugate (DS-TA) nanoparticles (NPs) for treating OA by specifically targeting scavenger receptor class A (SR-A) on activated macrophages. We verified the excellent targeting specificity of DS-TA NPs to SR-A by flow cytometry and confocal laser scanning microscopy. DS-TA NPs were found to effectively reduce the viability of activated macrophages (RAW 264.7 cells) and the expression of proinflammatory cytokines. Intra-articular injection of DS-TA NPs effectively alleviated the structural damages to the joint cartilage, as confirmed in histopathological analysis. Additionally, DS-TA NPs decreased the expression of proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, in the cartilage tissue. Thus, DS-TA NPs are a potential therapeutic nanomedicine for the targeted treatment of OA. |
Databáze: | OpenAIRE |
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