Hyaluronic acid–green tea catechin conjugates as a potential therapeutic agent for rheumatoid arthritis |
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Authors: | Fan Lee Ki Hyun Bae Shengyong Ng Atsushi Yamashita Motoichi Kurisawa |
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Affiliation: | Institute of Bioengineering and Bioimaging, 31 Biopolis Way, The Nanos, Singapore 138669 Singapore, Fax: +65-6478-9083, +65-6824-7139 |
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Abstract: | Fibroblast-like synoviocytes are a key effector cell type involved in the pathogenesis of rheumatoid arthritis. The major green tea catechin, epigallocatechin-3-O-gallate (EGCG), has attracted significant interest for rheumatoid arthritis therapy because of its ability to suppress the proliferation and interleukin-6 secretion of synoviocytes. However, therapeutic efficacy of EGCG has been limited by a lack of target cell specificity. Herein we report hyaluronic acid–EGCG (HA–EGCG) conjugates as an anti-arthritic agent that is capable of targeting fibroblast-like synoviocytes via HA–CD44 interactions. These conjugates exhibited superior anti-proliferative and anti-inflammatory activities compared with EGCG under simulated physiological conditions. Near-infrared fluorescence imaging revealed preferential accumulation of the conjugates at inflamed joints in a collagen-induced arthritis rat model, and their anti-arthritic efficacy was investigated by measuring a change in the edema and histopathological scores. Our findings suggest the potential of HA–EGCG conjugates as an anti-arthritic agent for the treatment of rheumatoid arthritis.Macromolecular HA–EGCG conjugates undergo targeted internalization by CD44-overexpressing fibroblast-like synoviocytes and subsequently cause H2O2-induced cell death and inhibition of IL-6 secretion, thereby suppressing the progression of arthritis. |
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