Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis.
Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis.
复制标题
DOI：
10.1002/art.30459
复制
发表时间：
2011-09
影响因子：
--
通讯作者：
Baker, James R., Jr.
中科院分区：
文献类型：
--
作者：
Thomas, Thommey P.;Goonewardena, Sascha N.;Majoros, Istvan J.;Kotlyar, Alina;Cao, Zhengyi;Leroueil, Pascale R.;Baker, James R., Jr.
目的：研究多价叶酸(FA)共价偶联的聚酰胺胺(G5)树枝状大分子纳米粒子(G5-FA-MTX)对巨噬细胞的靶向摄取，以及FA-甲氨蝶呤(G5-FA-MTX)对关节炎炎性疾病的治疗作用。利用流式细胞术和共聚焦显微镜，在巨噬细胞系和分离的小鼠巨噬细胞中进行了体外研究，以检查细胞对荧光标记的G5-FA纳米颗粒的摄取。在胶原性关节炎大鼠模型上进行了体内研究，以评估G5-FA-MTX的治疗潜力。叶酸靶向树枝状大分子以受体特异性的方式结合并内化到表达叶酸受体β的巨噬细胞系和原代小鼠巨噬细胞中。G5-FA-MTX作为一种有效的抗炎剂，可以降低关节炎引起的炎症参数，如脚踝肿胀、足爪体积、软骨损伤、骨吸收和体重下降。使用叶酸靶向纳米颗粒将MTX特异性靶向巨噬细胞，可能为类风湿关节炎的抗炎治疗提供一种有效的临床方法。
To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 (G5)) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and the activity of a FA- and methotrexate-conjugated dendrimer (G5-FA-MTX) as a therapeutic for the inflammatory disease of arthritis. In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescently tagged G5-FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen-induced arthritis to evaluate the therapeutic potential of G5-FA-MTX. Folate targeted dendrimer bound and internalized in a receptor-specific manner into both folate receptor β-expressing macrophage cell lines and primary mouse macrophages. The G5-FA-MTX acts as a potent anti-inflammatory agent and reduces arthritis-induced inflammatory parameters such as ankle swelling, paw volume, cartilage damage, bone resorption and body weight decrease. The use of folate-targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for anti-inflammatory therapy in rheumatoid arthritis.
登录
查看更多内容
影响因子：
2.9
作者：
Grabar, Petra Bohanec;Logar, Dusan;Dolzan, Vita
通讯作者：
Dolzan, Vita
影响因子：
5.5
作者：
Majoros, IJ;Keszler, B;Baker, JR
通讯作者：
Baker, JR
影响因子：
11.2
作者：
Kukowska-Latallo, JF;Candido, KA;Baker, JR
通讯作者：
Baker, JR
DOI：
10.1007/bf01972818
发表时间：
1989-06-01
期刊：
AGENTS AND ACTIONS
影响因子：
--
作者：
JAFFEE, BD;KERR, JS;ACKERMAN, NR
通讯作者：
ACKERMAN, NR
影响因子：
5.5
作者：
Maetzel, A;Wong, A;Bombardier, C
通讯作者：
Bombardier, C