Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis
Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis
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DOI：
10.1016/j.biomaterials.2017.03.044
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发表时间：
2017-07-01
期刊：
影响因子：
14
通讯作者：
Park, Jae Hyung
中科院分区：
文献类型：
--
作者：
Heo, Roun;You, Dong Gil;Park, Jae Hyung
为了开发用于将甲氨蝶呤（MTX）靶向递送至类风湿性关节炎（RA）中的发炎关节的纳米颗粒，通过将5 β-胆烷酸缀合至硫酸葡聚糖（DS）骨架来合成两亲性多糖。由于其两亲性，DS衍生物在水性条件下自组装成球形纳米颗粒（直径220 nm）。通过简单的透析方法，MTX被有效地负载到DS纳米粒中（负载效率：73.0%）。有趣的是，DS纳米颗粒通过清道夫受体A类介导的内吞作用被活化的巨噬细胞选择性摄取，巨噬细胞负责炎症和关节破坏。当全身给予实验性胶原诱导关节炎（CIA）小鼠时，DS纳米颗粒有效地在炎症关节中蓄积（比野生型小鼠（WT）高12倍），这意味着它们对RA组织的高靶向性。此外，与单独的游离MTX相比，MTX负载的DS纳米颗粒在小鼠中表现出对CIA的显著改善的治疗功效。总体而言，这里提供的数据表明，DS纳米颗粒是潜在的有用的纳米药物RA成像和治疗。(C)2017爱思唯尔有限公司版权所有
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. (C) 2017 Elsevier Ltd. All rights reserved.