Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis
- Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis
- 권익찬; 김광명; 최기영; 전상민; 엄우람; 허로운; 유동길; 박종성; 최유리; 권승리; 조동규; 강영모; 박재형
- Dextran sulfate; Nanoparticles; Drug delivery; Macrophage; Rheumatoid arthritis
- Issue Date
- VOL 131-26
- 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 5 beta-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.
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