In rheumatoid arthritis (RA), insufficient apoptosis of macrophages and excessive generation of pro-inflammatory cytokines are intimately connected, accelerating the development of disease. Here, a fluorinated polyamidoamine dendrimer (FP) is used to deliver miR-23b to reduce inflammation by triggering the apoptosis of as well as inhibiting the inflammatory response in macrophages. Following the intravenous injection of FP/miR-23b nanoparticles in experimental RA models, the nanoparticles show therapeutic efficacy with inhibition of inflammatory response, reduced bone and cartilage erosion, suppression of synoviocyte infiltration and the recovery of mobility. Moreover, the nanoparticles accumulate in the inflamed joint and are non-specifically captured by synoviocytes, leading to the restoration of miR-23b expression in the synovium. The miR-23b nanoparticles target Tab2, Tab3 and Ikka to regulate the activation of NF-κB pathway in the hyperplastic synovium, thereby promoting anti-inflammatory and anti-proliferative responses. Additionally, the intravenous administration of FP/miR-23b nanoparticles do not induce obvious systemic toxicity. Overall, our work demonstrates that the combination of apoptosis induction and inflammatory inhibition could be a promising approach in the treatment of RA and possibly other autoimmune diseases.

在类风湿关节炎（RA）中，巨噬细胞凋亡不足与促炎细胞因子的过度生成密切相关，加速了疾病的发展。在这里，氟化聚酰胺胺树枝状聚合物 (FP) 用于传递 miR-23b，通过触发巨噬细胞的细胞凋亡和抑制巨噬细胞的炎症反应来减少炎症。在实验性 RA 模型中静脉注射 FP/miR-23b 纳米颗粒后，纳米颗粒显示出抑制炎症反应、减少骨和软骨侵蚀、抑制滑膜细胞浸润和恢复活动性的治疗功效。此外，纳米颗粒积聚在发炎的关节中，并被滑膜细胞非特异性捕获，导致滑膜中 miR-23b 表达的恢复。Tab2、Tab3和Ikka调节增生性滑膜中 NF-κB 通路的激活，从而促进抗炎和抗增殖反应。此外，FP/miR-23b 纳米颗粒的静脉内给药不会引起明显的全身毒性。总的来说，我们的工作表明，细胞凋亡诱导和炎症抑制的结合可能是治疗 RA 和可能的其他自身免疫性疾病的一种有前途的方法。