earticle

영어

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which the white blood cells interact with antigen-derived immune complexes, causing an influx and activation of lymphocytes and monocytes via increased vascularization [1-3]. Activated macrophages, over-expressing scavenger receptor type A (SR-A), are the attractive therapeutic target for rheumatoid arthritis (RA) since they play a vital role in the cartilage and bone destruction. In an attempt to develop self-assembled nanoparticles (NPs) for targeting RA, we prepared the amphiphilic copolymer via click chemistry, composed of the hydrophilic dextran sulfate (DS) as the ligand for SR-A and polycaprolactone (PCL) as the hydrophobic segment. The copolymer formed spherical NPs (200 nm in diameter) with the negatively charged surface in a physiological solution. The DS-b-PCL NPs were effectively taken up by lipopolysaccharide-activated macrophages (RAW 264.7 cells), whereas they were rarely internalized into free DS-treated cells, implying efficient cellular uptake of the DS-NPs by receptor-mediated endocytosis. Following systemic administration of Cy5.5-labeled DS-b-PCL NPs into the collagen-induced arthritis (CIA) mice, their biodistribution was monitored as a function of time using a non-invasive near-infrared fluorescence imaging system. It was confirmed that DS-b-PCL NPs were selectively accumulated into the joint site of the CIA mice. Histological analysis demonstrated colocalization of DS-NPs and SR-A in the synovial tissue of the CIA mice. These results imply that the DS-NPs are highly useful as the constituents of formulations for diagnosis and therapy of RA.