title: Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis.
abstract: With the aim of developing nanoparticles for targeted delivery of methotrexate (MTX) to inflamed joints in rheumatoid arthritis (RA), an amphiphilic polysaccharide was synthesized by conjugating 5β-cholanic acid to a dextran sulfate (DS) backbone. Due to its amphiphilic nature, the DS derivative self-assembled into spherical nanoparticles (220 nm in diameter) in aqueous conditions. The MTX was effectively loaded into the DS nanoparticles (loading efficiency: 73.0%) by a simple dialysis method. Interestingly, the DS nanoparticles were selectively taken up by activated macrophages, which are responsible for inflammation and joint destruction, via scavenger receptor class A-mediated endocytosis. When systemically administrated into mice with experimental collagen-induced arthritis (CIA), the DS nanoparticles effectively accumulated in inflamed joints (12-fold more than wild type mice (WT)), implying their high targetability to RA tissues. Moreover, the MTX-loaded DS nanoparticles exhibited significantly improved therapeutic efficacy against CIA in mice compared to free MTX alone. Overall, the data presented here indicate that DS nanoparticles are potentially useful nanomedicines for RA imaging and therapy.
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea.
authors.forename: Roun
authors.initials: R
authors.lastname: Heo
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea; Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
authors.forename: Dong Gil
authors.initials: DG
authors.lastname: You
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea; Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
authors.forename: Wooram
authors.initials: W
authors.lastname: Um
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Jeon
authors.affiliation: Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore 21231, United States.
authors.forename: Jong-Sung
authors.initials: JS
authors.lastname: Park
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Choi
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Seunglee
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Dong-Gyu
authors.initials: DG
authors.lastname: Jo
authors.affiliation: School of Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Republic of Korea; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: jhpark1@skku.edu.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy*; D016264:Dextran Sulfate / Q000032:analysis*; D004337:Drug Carriers / Q000032:analysis*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D053758:Nanoparticles / Q000032:analysis*; D061848:Optical Imaging; D000067996:RAW 264.7 Cells; D000068936:Theranostic Nanomedicine
chemical_list: D018501:Antirheumatic Agents; D004337:Drug Carriers; D016264:Dextran Sulfate; D008727:Methotrexate
keywords: Dextran sulfate; Drug delivery; Macrophage; Nanoparticles; Rheumatoid arthritis