College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
Oncology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
J Control Release. 2022 May;345:851-879. doi: 10.1016/j.jconrel.2022.04.001. Epub 2022 Apr 6.
Rheumatoid arthritis (RA) is a complicated autoimmune disease that results in severe joint inflammation, synovial hyperplasia, pannus formation, cartilage and bone destruction, and other RA-associated complications. Although the pathogenesis of RA remains unclear, increasing reports have shown that inflammation-relevant cells and the microenvironment of inflamed joints play a critical role in the formation and aggravation of RA. Recently, numerous nanotherapeutics have been engineered to overcome these intractable challenges by readjusting inflammation-related seeds (endothelial cells, macrophages, neutrophils, antigen-presenting cells, fibroblasts, osteoclasts, T cells, B cells, and chondrocytes) and inflamed soils (NO, cell-free DNA, hypoxia, ROS, and pro-inflammatory cytokines). In this review, we first present a detailed pathogenesis of RA, with an emphasis on the emerging advances in regulating seeds or remodeling soils for RA treatment. We then outline these intelligent therapeutics via synergistic seed-soil adjustment, particularly for spatiotemporally cascade-responsive or all-in-one integrational nanosystems. Finally, we briefly discuss the ongoing challenges and prospects for the clinical development and translation of seed soil-based therapies.
类风湿关节炎（RA）是一种复杂的自身免疫性疾病，可导致严重的关节炎症、滑膜增生、血管翳形成、软骨和骨破坏以及其他与 RA 相关的并发症。虽然 RA 的发病机制仍不清楚，但越来越多的报告表明，炎症相关细胞和炎症关节的微环境在 RA 的形成和加重中起着关键作用。最近，许多纳米疗法被设计用来通过调整炎症相关种子（内皮细胞、巨噬细胞、中性粒细胞、抗原呈递细胞、成纤维细胞、破骨细胞、T 细胞、B 细胞和软骨细胞）和炎症土壤（NO、无细胞 DNA、缺氧、ROS 和促炎细胞因子）来克服这些棘手的挑战。在这篇综述中，我们首先详细介绍了 RA 的发病机制，重点介绍了调节种子或重塑 RA 治疗土壤的新进展。然后，我们通过协同的种子-土壤调节来概述这些智能疗法，特别是针对时空级联反应或一体化的纳米系统。最后，我们简要讨论了基于种子土壤的疗法在临床开发和转化方面的当前挑战和前景。
