Rheumatoid arthritis (RA) is a chronicautoimmune disease, marked by joint swelling and pain, articular synovial hyperplasia, as well as cartilage and bone destruction. Triptolide (TP) is an anti-inflammatory molecule but its use to treat RA is limited due to poor solubility and extremely high toxicity. In this study, by encapsulating TP into a star-shaped amphiphilic block copolymer, POSS-PCL-b-PDMAEMA, we engineered a pH-sensitive TP-loaded nanomedicine (TP@NPs) to simultaneously reduce the toxicity of TP and improve its therapeutic efficacy. TP@NPs shows a uniform spherical structure with a hydrodynamic diameter of ~92 nm and notable pH-responsiveness. In vitro TP@NPs showed reduced cytotoxicity and cell apoptosis of treated RAW264.7 cells compared to free TP. And in vivo intravenous injection of indocyanine green-labeled NPs into a collagen-induced arthritis model in mice showed that the engineered compound had potent pharmacokinetic and pharmacodynamic profiles, while exhibiting significant cartilage-protective and anti-inflammatory effects with a better efficacy and neglible systemic toxicity even at an ultralow dose compared to free TP. These results suggest that TP@NPs may be a safe and effective therapy for RA and other autoimmune diseases.

类风湿关节炎（RA）是一种慢性自身免疫性疾病，以关节肿胀和疼痛，关节滑膜增生以及软骨和骨破坏为特征。雷公藤内酯醇（TP）是一种抗炎分子，但由于溶解性差和毒性极高，其用于RA的用途受到限制。在这项研究中，通过将TP封装到星形两亲嵌段共聚物POSS-PCL-b-PDMAEMA中，我们设计了一种pH敏感的TP负载纳米药物（TP @ NPs），以同时降低TP的毒性并改善其治疗效果。功效。TP @ NPs具有均匀的球形结构，流体动力学直径约为92 nm，并且具有明显的pH响应性。与游离TP相比，处理后的RAW264.7细胞的体外TP @ NPs降低了细胞毒性和细胞凋亡。和体内将吲哚菁绿标记的NPs静脉注射到胶原蛋白诱发的小鼠关节炎模型中表明，该工程化合物具有有效的药代动力学和药效学特征，同时表现出显着的软骨保护和抗炎作用，即使在50℃时仍具有更好的功效和可忽略的全身毒性与游离TP相比超低剂量。这些结果表明，TP @ NPs对于RA和其他自身免疫性疾病可能是一种安全有效的疗法。