假体周围骨溶解引起的假体无菌性松动是人工关节置换术（TJA）最主要的并发症，常致使患者必须接受翻修手术，目前缺乏有效的药物延缓假体周围骨溶解的病理进程。研究发现姜黄素能通过抑制核因子κB抑制蛋白激酶（IKK）的作用，抑制整个NF-κB信号通路的活化，从而对骨转移瘤，牙周炎等疾病引起的骨溶解和骨丢失起到一定的治疗效果。本课题假说姜黄素可通过抑制IKK的作用有效延缓颗粒诱导骨溶解的产生；并拟制备一种新型双靶向的载药纳米粒，以载姜黄素的PLGA作为纳米粒的外壳，外壳内添加超顺磁性氧化铁，外壳表面偶联唑来膦酸，从而使其在外加磁场的作用下，具备唑来膦酸主动靶向和磁场引导被动靶向能力。从体内、体外不同方面评价这种新型载药纳米粒对颗粒诱导骨溶解的治疗效果，以及对骨组织的靶向能力。本课题将阐明姜黄素治疗颗粒诱导骨溶解的作用机制，并为实现TJA术后假体周围骨溶解的靶向治疗提供新的方法和思路。

Aseptic loosening induced by periprosthetic osteolysis (PPO) is the leading complication of total joint arthroplasty (TJA), which makes patients have to accept revision surgery. No drug can effectively prevent or even slow down the pathological process at present. Recent studies showed curcumin can inhibit the whole activation of NF-κB signal pathway through inhibiting the IκB kinase (IKK); therefore it had the ability for the treatment of the osteolysis and bone loss induced by bone metastatic cancer and dentoalveolitis. This project hypothesizes that curcumin can inhibit the osteolysis induced by wear debris by inhibiting the IKK，and intend to prepare a novel dual targeting drug carrying nanoparticle. The nanoparticle was made by poly lactic-co-glycolic acid (PLGA) as the shell with curcumin on the surface; the PLGA shell was contained superparamagnetic iron oxide (SPIO) and coated with zoledronic acid. The nanoparticles had active targeting ability guided by zoledronic acid and passive targeting ability guided by SPIO under the action of magnetic field. The therapeutic effect to the osteolysis induced by wear debris and the targeting ability to the bone tissue of the novel drug carrying on nanoparticles were evaluated by in vitro and vivo experiments. This project will illustrate the mechanism of curcumin for the treatment of osteolysis induced by wear debris, and provide a novel method for targeting treatment for periprosthetic osteolysis after total joint arthroplasty.