类风湿关节炎(RA)是一种以关节滑膜炎、血管翳新生、骨破坏为基本病理改变的的高度致残性自身免疫性疾病，其治疗首选药甲氨蝶呤(MTX) 因有肝功损害、骨髓抑制等副作用常导致临床干预停止而发展为难治性RA。如何在非关节腔穿刺情况下实现病变关节的可视化精准靶向用药与疗效评估，减少全身用药量，降低副作用，缩短疗程是RA治疗的难点问题。本项目拟利用具有高载药量并可超声定点释药的声敏脂质体，借助可靶向滑膜血管内皮细胞整合素αvβ3受体并能加速药物递送的穿膜肽iRGD和MR造影剂超小超顺磁性氧化铁粒子(USPIO)，构建iRGD修饰的载USPIO和MTX声敏脂质体靶向传递体系，集MR分子成像和低频超声定点控释药物这两种无创技术于一体，有望实现MR分子成像引导下超声定点控释药物、可视化靶向治疗RA和疗效监测。我们前期初步证实靶向iRGD-MTX-脂质体治疗RA小鼠的疗效显著优于非靶向组和游离MTX组。

Rheumatoid arthritis (RA) is a common severe autoimmune disease characterized by joint synovitis, pannus formation, bone destruction, with a high degree of disability. Althrough methotrexate (MTX) is widely accepted as the first choice of the drug for patients with rheumatoid arthritis, its side effects, such as hepatic lesion and myelosuppression, seriously affected the treatment of rheumatoid arthritis and eventually resulted in the discontinuation of clinical intervention and disease deterioration. It has become a difficult point of RA treatment to achieve the accurate targeting drug and response evaluation, reduce systemic dosage, relieve side effects, shorten the course under the condition of noninvasive treatment. Interestingly, echogenic liposomes are ideal ultrasound-activated drug carriers due to their characteristics of high loading efficiency and ultrasound-controlled drug delivery, which can better achieve MR-guided local drug delivery with the aid of magnetic nanoparticles(USPIO). Meanwhile, iRGD is a cell-penetrating peptide which can target over-expressed αvβ3 receptors of RA synovial vascular endothelial cells and enhance drug delivery inside synovial tissue. This study intends to regard over-expressed αvβ3 receptors closely related to the pathogenesis of rheumatoid arthritis as the target, and synthesize iRGD-modified echogenic liposomes loading MTX and USPIO to integrate their advantages between MR molecular imaging and low frequency ultrasound-controlled drug delivery. This project is expected to combine MR molecular imaging guidance with ultrasound-assisted drug delivery to achieve visual targeting treatment of RA and to enhance the effect of drugs. In the preliminary experiment, we briefly confirmed the validity of iRGD-modified liposomes in the treatment of RA, which will further provide favorable conditions for our next experiment.