DEK protein is critical to the formation of neutrophil extracellular traps (NETs) in rheumatoid arthritis (RA). Blocking DEK using the aptamer DTA via articular injection has been shown to have robust anti-inflammatory efficacy in a previous study. However, DTA is prone to nuclease degradation and renal clearance in vivo. RA is a systemic disease that involves multiple joints, and local injection is impractical in clinical settings. In this study, DTA was modified with methoxy groups on all deoxyribose sugar units and inverted deoxythymidine on the 3′ end (DTA4) to enhance its stability against nuclease. DTA4 is stable for 72 h in 90% mouse serum and maintains a high binding affinity to DEK. DTA4 effectively inhibits the formation of NETs and the migration of HUVECs in vitro. DTA4 was then modified with cholesterol on its 5′ end to form DTA6. DTA6 dramatically reduces DEK expression in inflammatory RAW264.7 cells. A hydrogel microneedle (hMN) was then fabricated for the transdermal delivery of DTA6. The hMN maintains morphological integrity after absorbing the aptamer solution, effectively pierces the skin, and rapidly releases DTA6 into the dermis. The DTA6-loaded hMN significantly attenuates inflammation and protects joints from cartilage/bone erosion in collagen-induced arthritis (CIA) mice.

中文翻译：

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由水凝胶微针提供的新型 DEK 靶向适体可减轻胶原诱导的关节炎

DEK 蛋白对于类风湿性关节炎 (RA) 中中性粒细胞胞外陷阱 (NET) 的形成至关重要。在先前的研究中，通过关节注射使用适体 DTA 阻断 DEK 已被证明具有强大的抗炎功效。然而，DTA在体内容易发生核酸酶降解和肾脏清除。RA 是一种全身性疾病，涉及多个关节，局部注射在临床环境中是不切实际的。在这项研究中，DTA 在所有脱氧核糖单位上都被甲氧基修饰，在 3' 末端 (DTA4) 上用反向脱氧胸苷修饰，以增强其对核酸酶的稳定性。DTA4 在 90% 小鼠血清中可稳定 72 小时，并保持与 DEK 的高结合亲和力。DTA4在体外有效抑制NETs的形成和HUVECs的迁移. 然后在 DTA4 的 5' 端用胆固醇修饰 DTA4，形成 DTA6。DTA6 显着降低炎症性 RAW264.7 细胞中的 DEK 表达。然后制造水凝胶微针 (hMN) 用于 DTA6 的透皮递送。hMN在吸收适配体溶液后保持形态完整性，有效刺穿皮肤，并迅速将DTA6释放到真皮中。加载 DTA6 的 hMN 可显着减轻炎症并保护关节免受胶原诱导性关节炎 (CIA) 小鼠的软骨/骨侵蚀。