Suppression of human arthritis synovial fibroblasts inflammation using dexamethasone-carbon nanotubes via increasing caveolin-dependent endocytosis and recovering mitochondrial membrane potential
- Authors
- Lee, Yeon Kyung; Kim, Sang-Woo; Park, Jun-Young; Kang, Woong Chol; Kang, Youn Joo; Khang, Dongwoo
- Issue Date
- Aug-2017
- Publisher
- DOVE MEDICAL PRESS LTD
- Keywords
- carbon nanotubes; polyethylene-glycol; dexamethasone; arthritis; fibroblast-like synoviocytes; caveolin-dependent endocytosis
- Citation
- INTERNATIONAL JOURNAL OF NANOMEDICINE, v.12, pp.5761 - 5778
- Journal Title
- INTERNATIONAL JOURNAL OF NANOMEDICINE
- Volume
- 12
- Start Page
- 5761
- End Page
- 5778
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/7476
- DOI
- 10.2147/IJN.S142122
- ISSN
- 1178-2013
- Abstract
- Dexamethasone (DEX), a non-particulate glucocorticoid (GC) to inhibit anti-inflammatory response, has been widely used for the treatment of various diseases such as arthritis, cancer, asthma, chronic obstructive pulmonary disease, cerebral edema, and multiple sclerosis. However, prolonged and/or high-dose GC therapy can cause various serious adverse effects (adrenal insufficiency, hyperglycemia, Cushing's syndrome, osteoporosis, Charcot arthropathy, etc). In this study, developed DEX-carbon nanotube (CNT) conjugates improved intracellular drug delivery via increased caveolin-dependent endocytosis and ultimately suppressed the expression of major pro-inflammatory cytokines in tumor necrosis factor-alpha (TNF-alpha)stimulated human fibroblast-like synoviocytes (FLS) at low drug concentrations. Specifically, DEX on polyethylene-glycol (PEG)-coated CNTs induced caveolin uptake, recovered mitochondrial disruption, and inhibited reactive oxygen species production by targeting mitochondria that was released from the early endosome in TNF-alpha-stimulated FLS. The obtained results clearly demonstrated that DEX-PEG-coated CNTs significantly inhibited the inflammation by FLS in rheumatoid arthritis (RA) by achieving greater drug uptake and efficient intracellular drug release from the endosome, thus suggesting a mechanism of effective low-dose GC therapy to treat inflammatory diseases, including RA and osteoarthritis.
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