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Folate-Targeted Dendrimers Selectively Accumulate at Sites of Inflammation in Mouse Models of Ulcerative Colitis and Atherosclerosis
Biomacromolecules ( IF 6.2 ) Pub Date : 2017-09-14 00:00:00 , DOI: 10.1021/acs.biomac.7b00728
Scott Poh 1 , Karson S. Putt 2 , Philip S. Low 2, 3
Affiliation  

Folate-receptor-positive activated macrophages are critical for the development and maintenance of many chronic inflammatory and autoimmune diseases. Previously, small-molecule folate-targeted conjugates were found to specifically bind to these activated macrophages in vitro and selectively accumulate at sites of inflammation in vivo. While these small-molecule conjugates have shown promise, the use of a folate-targeted, higher cargo capacity nanovehicle may prove superior in delivering imaging or therapeutic agents in vivo. This nanoparticle strategy has been demonstrated in oncology, where targeted dendrimers have shown superior delivery capabilities; however, little research has been pursued in the area of folate-targeted dendrimers for inflammation and autoimmune diseases. Therefore, we endeavored to create a folate-decorated dendrimer to explore its uptake in mouse models of ulcerative colitis and atherosclerosis. We demonstrate that our final poly(ethylene glycol)-coated, acetic-anhydride-capped, folate-targeted poly(amidoamine) dendrimer exhibits no discernible cytotoxicity in vitro, specifically binds to a folate-receptor-expressing macrophage cell line in vitro, and selectively accumulates in areas of inflammation in vivo.

中文翻译:

在溃疡性结肠炎和动脉粥样硬化的小鼠模型中,叶酸靶向树状聚合物选择性地聚集在炎症部位。

叶酸受体阳性活化的巨噬细胞对于许多慢性炎性和自身免疫性疾病的发展和维持至关重要。以前,发现小分子以叶酸为靶标的结合物在体外与这些活化的巨噬细胞特异性结合,并选择性地在体内炎症部位蓄积。尽管这些小分子结合物已显示出希望,但以叶酸为靶标,具有更高载货量的纳米载体的使用可能证明在体内递送成像剂或治疗剂方面具有优势。这种纳米颗粒策略已在肿瘤学中得到证明,其中靶向树状聚合物显示出卓越的递送能力;然而,在针对叶酸的树枝状大分子用于炎症和自身免疫性疾病的领域中,尚未进行任何研究。所以,我们努力创建一种叶酸修饰的树状大分子,以探索其在溃疡性结肠炎和动脉粥样硬化小鼠模型中的摄取。我们证明了我们最终的聚乙二醇包被的,乙酸酐封端的,叶酸靶向的聚(酰胺基胺)树状大分子在体外没有表现出可辨别的细胞毒性,特别是在体外与表达叶酸受体的巨噬细胞系结合,并且在体内炎症区域选择性积聚。
更新日期:2017-09-15
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