Ultrasound-triggered perfluorocarbon-derived nanobombs for targeted therapies of rheumatoid arthritis
Ultrasound-triggered perfluorocarbon-derived nanobombs for targeted therapies of rheumatoid arthritis
复制标题
超声波触发的全氟化碳纳米炸弹用于类风湿性关节炎的靶向治疗
DOI：
10.1039/c9tb00978g
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发表时间：
2019-08-07
影响因子：
7
通讯作者：
Qiu, Li
中科院分区：
文献类型：
--
作者：
Zhu, Bihui;Wang, Liyun;Qiu, Li
为了满足日益增长的对更有效的类风湿性关节炎(RA)治疗的需求，出现了几种治疗剂和方法。然而，开发一种超声(US)响应的纳米系统用于治疗类风湿关节炎仍然充满挑战。在这里，美国触发的全氟化碳(PFC)为基础的“纳米弹”被报道用于RA的靶向治疗。采用薄膜水合和超声法制备了以全氟戊烷(PFP)为核心的负载糖皮质激素地塞米松(Dex)的纳米微滴(NDS)和叶酸(FA)接枝聚乙二醇化磷脂(PFP-Dex@NDS-PEG-FA)为外壳的靶向纳米颗粒。作为引发剂的1 MHz US可以引发纳米球的爆炸，促进药物的释放。高浓度的PFP-Dex@NDS-PEG-FA联合超声对激活的RAW264.7细胞的细胞毒性最高，而对激活的RAW264.7细胞的细胞摄取试验表明，FA修饰的纳米颗粒可以增加激活的RAW264.7细胞的摄取。此外，PFP-Dex@NDS-PEG-FA联合US对胶原性关节炎SD大鼠模型的滑膜炎和关节破坏有良好的抑制作用，是治疗RA的有效靶向药物。因此，在本研究中，靶向超声触发的PFC纳米球与US联合用于RA的治疗将提供一种新的治疗策略，从而在治疗药物和纳米药物治疗领域具有巨大的应用潜力。
Several kinds of therapeutic agents and methods are emerging to meet the increasing demand for a more effective rheumatoid arthritis (RA) therapy. However, developing an ultrasound (US)-responsive nanosystem for the treatment of RA is still filled with challenges. Herein, US-triggered perfluorocarbon (PFC)-based "nanobombs" are reported for the targeted treatment of RA. The targeted nanobombs were synthesized by a thin-film hydration and sonication method and had a core of perfluoropentane (PFP)-based nanodroplets (NDs) loaded with glucocorticoid dexamethasone (Dex) and a shell of folic acid (FA)-grafted polyethylene glycol (PEG)-functionalized phospholipid (PFP-Dex@NDs-PEG-FA). The 1 MHz US used as an initiator could trigger the "explosion" of nanobombs and enhance the drug release. The high concentration of PFP-Dex@NDs-PEG-FA with US showed the highest cytotoxicity on activated RAW264.7 cells, which were the main targeted cells in RA lesions, while the cellular uptake tests conducted on activated RAW264.7 cells demonstrated that the nanobombs modified with FA could increase the uptake of the activated RAW264.7 cells. Moreover, PFP-Dex@NDs-PEG-FA combined with US exhibited an excellent inhibition of synovitis and joint destruction in a collagen-induced arthritis SD rat model, acting as an efficient targeted agent for the RA therapy. Therefore, in this study, the targeted US-triggered PFC-based nanobombs with US used to treat the RA would offer a new treatment strategy and thus have a great potential for application in the areas of theranostic agents and nanomedicine treatment.