title: Targeting and liposomal drug delivery to CD40L expressing T cells for treatment of autoimmune diseases.
abstract: CD40L is considered as an important target for the treatment of autoimmune diseases. There have been many efforts devoted to the development of antibodies and other molecules to disrupt CD40/CD40L interaction for therapeutic benefits. In this study, we designed a CD40L specific peptide ligand - A25 based on CD40L crystal structure and molecular docking studies. Its binding affinity and specificity to CD40L were confirmed by Surface Plasmon Resonance (SPR) measurements. The peptide A25 was then conjugated on the surface of liposomes and shown to be able to mediate specific liposomal drug delivery to CD40L+ cells. Loaded with the cytostatic drug methotrexate (MTX), the A25 modified liposome could significantly reduce the CD40L+ cell ratios in the experimental autoimmune encephalomyelitis (EAE) mice, resulting in great improvement in clinical scores. Since CD40L+ cells are involved in the pathological development of many auto-immune diseases, A25 conjugated drug targeting systems may be useful for developing therapies that are more efficacies and with less side effects.
authors.affiliation: School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
authors.affiliation: School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Si
authors.affiliation: School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Peng
authors.affiliation: School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China.
authors.forename: Hailing
authors.initials: H
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Rui
authors.affiliation: School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China.
authors.forename: Qunli
authors.initials: Q
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China.
authors.forename: Lieyi
authors.initials: L
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Med-X Research Institute and School of Biomedical, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, PR China. Electronic address: yhxu@sjtu.edu.cn.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D001665:Binding Sites; D023201:CD40 Ligand / Q000737:chemistry / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D017076:Computer-Aided Design; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D019169:Jurkat Cells; D008024:Ligands; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D008810:Mice, Inbred C57BL; D062105:Molecular Docking Simulation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D020349:Surface Plasmon Resonance; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D008024:Ligands; D008055:Lipids; D008081:Liposomes; D010455:Peptides; D023201:CD40 Ligand; D008727:Methotrexate
keywords: Autoimmune disease; CD40L; Drug delivery; Liposome; Peptide ligand