De novo designed lipidated methotrexate was synthesized and self-assembled into microbubbles for targeted rheumatoid arthritis theranostic treatment. Controlled lipidatedmethotrexate delivery was achieved by ultrasound-targetedmicrobubble destruction technique. Methotrexate was dissociated inflammatory microenvironment of synovial cavity, owing to representive low pH and enriched leucocyte esterase. We first manipulated methotrexate controlled release with RAW 264.7 cell line in vitro and further verified with rheumatoid arthritis rabbits in vivo. Results showed that lipidated methotrexate microbubbles precisely affected infection focus and significantly enhanced rheumatoid arthritis curative effect comparing with dissociative methotrexate. This study indicates that lipidated methotrexate microbubbles might be considered as a promising rheumatoid arthritis theranostics medicine.

中文翻译：

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脂化甲氨蝶呤微泡：一种有前途的类风湿性关节炎治疗药物，通过超声波照射进行操作。

从头设计的脂化甲氨蝶呤被合成并自组装成微泡，用于靶向类风湿性关节炎治疗。通过超声靶向微泡破坏技术实现受控的脂化甲氨蝶呤递送。由于具有代表性的低 pH 值和富集的白细胞酯酶，甲氨蝶呤是分离的滑膜腔炎症微环境。我们首先在体外用 RAW 264.7 细胞系操纵甲氨蝶呤控释，并在体内用类风湿关节炎兔进一步验证. 结果表明，脂化甲氨蝶呤微泡精确影响感染灶，与游离甲氨蝶呤相比，显着提高类风湿关节炎的疗效。该研究表明，脂化甲氨蝶呤微泡可能被认为是一种有前途的类风湿关节炎治疗诊断药物。