Abstract：
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and inflammatory cellular infiltration. Functional cells in the RA microenvironment (RAM) are composed of activated immune cells and effector cells. Activated immune cells, including macrophages, neutrophils, and T cells, can induce RA. Effector cells, including synoviocytes, osteoclasts, and chondrocytes, receiving inflammatory stimuli, exacerbate RA. These functional cells, often associated with the upregulation of surface-specific receptor proteins and significant homing effects, can secrete pro-inflammatory factors and interfere with each other, thereby jointly promoting the progression of RA. Recently, some nanomedicines have alleviated RA by targeting and modulating functional cells with ligand modifications, while other nanoparticles whose surfaces are camouflaged by membranes or extracellular vesicles (EVs) of these functional cells target and attack the lesion site for RA treatment. When ligand-modified nanomaterials target specific functional cells to treat RA, the functional cells are subjected to attack, much like the intended targets. When functional cell membranes or EVs are modified onto nanomaterials to deliver drugs for RA treatment, functional cells become the attackers, similar to arrows. This study summarized how diversified functional cells serve as targets or arrows by engineered nanoparticles to treat RA. Moreover, the key challenges in preparing nanomaterials and their stability, long-term efficacy, safety, and future clinical patient compliance have been discussed here.
摘要：
类风湿性关节炎(RA)是一种以滑膜炎症和炎性细胞浸润为特征的慢性系统性自身免疫性疾病。RA微环境(RAM)中的功能细胞由活化的免疫细胞和效应细胞组成。激活的免疫细胞，包括巨噬细胞,中性粒细胞，T细胞,可诱发RA。效应细胞,包括滑膜细胞,破骨细胞,和软骨细胞，接受炎症刺激，加重RA。这些功能细胞，通常与表面特异性受体蛋白的上调和显着的归巢效应有关，可以分泌促炎因子并相互干扰，从而共同促进RA的进展。最近,一些纳米药物通过配体修饰靶向和调节功能细胞来缓解RA，而表面被这些功能细胞的膜或细胞外囊泡（EV）掩盖的其他纳米颗粒靶向并攻击RA治疗的病变部位。当配体修饰的纳米材料靶向特定功能细胞治疗RA时，功能细胞受到攻击，很像预定的目标。当功能性细胞膜或EV被修饰到纳米材料上以递送用于RA治疗的药物时，功能细胞成为攻击者，类似于箭头。这项研究总结了多样化的功能细胞如何通过工程纳米颗粒作为靶标或箭头来治疗RA。此外，制备纳米材料及其稳定性的关键挑战，长期疗效，安全,和未来的临床患者依从性已经在这里讨论。
