Targeted delivery of nano-encapsulated anti-inflammatory agent represents a promising while challenging strategy in the treatment of rheumatoid arthritis (RA). Pro-inflammatory macrophages play a major role in the pathogenesis of RA. In this study, we investigated the effect of a macrophage-targeted pH-sensitive nanoparticle on collagen-induced arthritis (CIA) in mice. To target macrophage, all-trans-retinal was conjugated into dextran backbone through pH-sensitive hydrazone bond, then grafted with galactose (GDR). This nanoparticle was used for the encapsulation of triptolide (TPT), a potent anti-inflammatory compound isolated from Chinese herb. As expected, GDR nanoparticles preferentially accumulated in the inflammatory tissues. Treatment with GDR-TPT nanoparticles resulted in a marked decrease in the infiltration of CD3+ T cells and F4/80+ macrophages and reduction of the expression of TNF-α, IL-6 and IL-1β in the inflamed lesions of CIA mice. Furthermore, Th1 and Th17 responses were also inhibited. Importantly, anti-arthritic effect of TPT was markedly enhanced while its toxic effect was attenuated by encapsulating with GDR. GDR by itself also had moderate effect in the inhibition of arthritis, due to its intrinsic anti-inflammatory property. Therefore, our results clearly show that GDR-TPT nanoparticle may represent a promising drug delivery system for the treatment of RA.

中文翻译：

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封装在炎症靶向纳米颗粒中的全反式视网膜和雷公藤内酯醇对小鼠胶原诱导的关节炎的协同作用。

在类风湿关节炎（RA）的治疗中，纳米囊状抗炎药的靶向递送代表了一种有前途而又具有挑战性的策略。促炎性巨噬细胞在RA的发病机理中起主要作用。在这项研究中，我们调查了针对巨噬细胞的pH敏感纳米颗粒对小鼠胶原诱导的关节炎（CIA）的影响。为了靶向巨噬细胞，将全反式视网膜通过pH敏感的键缀合到葡聚糖骨架中，然后接枝半乳糖（GDR）。该纳米颗粒用于封装雷公藤甲素（TPT），这是一种从中草药中分离出来的有效抗炎化合物。如预期的那样，GDR纳米颗粒优先聚集在炎症组织中。用GDR-TPT纳米颗粒处理导致CIA小鼠发炎性病变中CD3 + T细胞和F4 / 80 +巨噬细胞的浸润显着减少，并且TNF-α，IL-6和IL-1β的表达降低。此外，Th1和Th17反应也被抑制。重要的是，TPT的抗关节炎作用显着增强，而其毒性作用通过用GDR封装而减弱。由于其固有的抗炎特性，GDR本身在抑制关节炎方面也具有中等作用。因此，我们的结果清楚地表明，GDR-TPT纳米颗粒可能代表了一种有前途的药物治疗RA的给药系统。通过GDR封装，TPT的抗关节炎作用显着增强，而其毒性作用减弱。由于其固有的抗炎特性，GDR本身在抑制关节炎方面也具有中等作用。因此，我们的结果清楚地表明，GDR-TPT纳米颗粒可能代表了一种有前途的药物治疗RA的给药系统。通过GDR封装，TPT的抗关节炎作用显着增强，而其毒性作用减弱。由于其固有的抗炎特性，GDR本身在抑制关节炎方面也具有中等作用。因此，我们的结果清楚地表明，GDR-TPT纳米颗粒可能代表了一种有前途的药物治疗RA的给药系统。