title: Multivalent structure of galectin-1-nanogold complex serves as potential therapeutics for rheumatoid arthritis by enhancing receptor clustering.
abstract: Cellular behaviour is controlled by numerous processes, including intracellular signalling pathways that are triggered by the binding of ligands with cell surface receptors. Multivalent ligands have multiple copies of a recognition element that binds to receptors and influences downstream signals. Nanoparticle-ligand complexes may form multivalent structures to crosslink receptors with high avidity and specificity. After conjugation onto gold nanoparticles, galectin-1 (Au-Gal1) bound with higher affinity to Jurkat cells to promote CD45 clustering and inhibition of its phosphatase activity, resulting in enhancement of apoptosis via caspase-dependent pathways. Au-Gal1 injected intra-articularly into rats with collagen-induced arthritis (CIA) promoted apoptosis of CD4+ T cells and reduced pro-inflammatory cytokine levels in the ankle joints as well as ameliorated clinical symptoms of arthritis. These observed therapeutic effects indicate that the multivalent structure of nanoparticle-ligands can regulate the distribution of cell surface receptors and subsequent intracellular signalling, and this may provide new insights into nanoparticle applications.
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Microbiology and Immunology, National Cheng Kung University Medical College, 1 University Road, Tainan 70101, Taiwan.
authors.forename: Yen-Jang
authors.initials: YJ
authors.lastname: Huang
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: Shiau
authors.forename: Shih-Yao
authors.initials: SY
authors.lastname: Chen
authors.forename: Yuh-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Chrong-Reen
authors.initials: CR
authors.lastname: Wang
authors.forename: Chiau-Yuang
authors.initials: CY
authors.lastname: Tsai
authors.forename: Meng-Ya
authors.initials: MY
authors.lastname: Chang
authors.forename: Yuan-Tsung
authors.initials: YT
authors.lastname: Li
authors.forename: Chia-Hsing
authors.initials: CH
authors.lastname: Leu
authors.forename: Chao-Liang
authors.initials: CL
authors.lastname: Wu
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000000981:diagnostic imaging / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D037483:Galectin 1 / Q000008:administration & dosage* / Q000737:chemistry; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007270:Injections, Intra-Articular; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016207:Cytokines; D037483:Galectin 1; D011956:Receptors, Cell Surface; D006046:Gold