载IR-820相变型纳米粒双模态成像及其对类风湿关节炎成纤维样滑膜细胞光动力效应的体外研究  

IR-820 loaded phase transition nanoparticles for dual-modal imaging and photodynamic effect on fibroblast-like synoviocytes of rheumatoid arthritis in vitro

作　　者：梁竹西 何欣雨 常淑芳[2] 王志刚 郝兰 李发琪 朱深银[1] Liang Zhu-Xi;He Xin-Yu;Chang Shu-Fang;Wang Zhi-Gang;Hao Lan;Li Fa-Qi;Zhu Shen-Yin(Department of Pharmacy,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China;Department of Obstetrics and Gynecology,the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China;Chongqing Key Laboratory of Ultrasound Molecular Imaging,Chongqing 400010,China)

机构地区：[1]重庆医科大学附属第一医院药学部,重庆400016 [2]重庆医科大学附属第二医院妇产科,重庆400010 [3]超声分子影像学重庆市医学重点实验室,重庆400010

出　　处：《解放军医学杂志》2021年第5期425-431,共7页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(81972439);重庆市基础研究与前沿探索项目(cstc2018jcyjAX0223)。

摘　　要：目的探讨载IR-820及全氟正戊烷(PFP)的相变型多功能分子影像探针(IR-820/PFP@PLGA)在体外的超声/光声双模态显像特性及其对类风湿关节炎成纤维样滑膜细胞的光动力效应。方法采用双乳化法制备IR-820/PFP@PLGA纳米粒,检测其基本表征、热致相变及光热效应,观察该纳米粒在体外的超声/光声双模态成像能力,评估其活性氧生成能力,采用CCK-8法和流式细胞术观察纳米粒对成纤维样滑膜细胞的光动力治疗效果。结果制备出的IR-820/PFP@PLGA纳米粒呈墨绿色,粒径为(261.8±3.2)nm,电位为(–27.4±0.7)mV,大小较均一,形态较规则;纳米粒经热处理后体积明显增大。经激光辐照后,纳米粒溶液温度上升,且与浓度呈正相关,并可观察到其超声成像明显增强;同时纳米粒的光声成像效果与其浓度呈线性相关;单线态荧光(SOSG)法检测显示纳米粒在激光辐照后产生大量活性氧并具有辐照时间依赖性。体外细胞实验发现,纳米粒具有良好的生物安全性,而在激光辐照后其细胞毒性随浓度升高而增加,并可引起明显的细胞凋亡。结论IR-820/PFP@PLGA纳米粒具有良好的体外双模态成像能力及对成纤维样滑膜细胞的光动力效应,可为类风湿关节炎诊疗一体化提供新的思路。Objective To investigate the photodynamic effect of IR-820 and perfluoropentane(PFP)loaded phasetransition multifunctional molecular imaging probe(IR-820/PFP@PLGA NPs)on ultrasound/photoacoustic dual-mode imaging and fibroblast-like synoviocytes(FLSs)of rheumatoid arthritis(RA)in vitro.Methods The IR-820/PFP@PLGA nanoparticles were prepared by double emulsification method.The basic characteristics,thermal phase transition and photothermal effect of IR-820/PFP@PLGA nanoparticles were determined,the ultrasound/photoacoustic dual-mode imaging ability in vitro of the IR-820/PFP@PLGA nanoparticles were observed,and the generation of reactive oxygen species in vitro were evaluated.The photodynamic therapy effect of the nanoparticles on fibroblast-like synoviocytes was observed by CCK-8 method and flow cytometry.Results The prepared IR-820/PFP@PLGA nanoparticles were dark green,with a particle size of(261.8±3.2)nm and a potential of(–27.4±0.7)mV.The size of the IR-820/PFP@PLGA nanoparticles were uniform and the morphology were regular.The size of nanoparticles and the temperature of nanoparticle solution increased obviously by laser irradiation,it was positively correlated with the concentration of nanoparticles,and enhanced ultrasound imaging was observed.The photoacoustic imaging effect of nanoparticle was linearly correlated with the concentration of IR-820/PFP@PLGA nanoparticles;The singlet oxygen sensor green(SOSG)assay revealed that the nanoparticles produced a large amount of reactive oxygen species after laser irradiation with timedependent manner;it was found by in vitro cell experiments that the nanoparticles had good biological safety,while the cytotoxicity increased along with the advanced nanoparticle concentration after laser irradiation,and also the apoptosis increased significantly.Conclusion IR-820/PFP@PLGA nanoparticles have a good dual-mode imaging and photodynamic effect on FLSs,which can provide a new idea for the integration of diagnosis and treatment for RA.

关 键 词：纳米粒 双模态成像 光动力治疗 新吲哚菁绿 全氟正戊烷 成纤维样滑膜细胞 

分 类 号：R593.22[医药卫生—内科学]