School of Materials Science and Engineering, and Center of Functional Biomaterials, Key Laboratory of Polymeric Composite Materials and Functional Materials of Ministry of Education, GD Research Center for Functional Biomaterials Engineering and Technology, Sun Yat-sen University, Guangzhou, 510275, China.
Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
Angew Chem Int Ed Engl. 2019 Mar 22;58(13):4254-4258. doi: 10.1002/anie.201813362. Epub 2019 Feb 18.
Cell-free deoxyribonucleic acid (cfDNA) released from either dead or damaged cells serves as a key autoantigen in rheumatoid arthritis (RA). They can be recognized by nucleic acid (NA) sensors such as the toll-like receptor (TLR), leading to activation of the innate immune system and chronic inflammation. Developed here is a cationic molecular scavenger, by screening cationic dendronized polymers, which eliminates cfDNA and inhibits TLR recognition and nucleic-acid-induced inflammation. The structure-property study demonstrates that toxicity, NA binding capacity, and biodistribution could be balanced to achieve maximum therapeutic effect by exquisite control of the molecular structure. In addition, the optimized cationic polymer effectively inhibited joint swelling, synovial hyperplasia, and bone destruction in collagen-induced arthritis (CIA) rat models. The results offer support for synthetic polymers offering new paradigm in autoimmune disease treatment.
细胞外游离脱氧核糖核酸 (cfDNA) 来源于死亡或受损的细胞，是类风湿关节炎 (RA) 的关键自身抗原。它们可以被核酸 (NA) 传感器如 Toll 样受体 (TLR) 识别，导致先天免疫系统的激活和慢性炎症。本文通过筛选阳离子化树状聚合物开发了一种阳离子分子清除剂，该清除剂可以清除 cfDNA 并抑制 TLR 识别和核酸诱导的炎症。结构-性能研究表明，通过精细控制分子结构，可以平衡毒性、NA 结合能力和生物分布，以达到最大的治疗效果。此外，优化的阳离子聚合物有效地抑制了胶原诱导关节炎 (CIA) 大鼠模型中的关节肿胀、滑膜增生和骨破坏。这些结果为合成聚合物在自身免疫性疾病治疗中提供了新的范例。
