袁勋,鞠丰翼,张玙,乔斌,王志刚,杜之渝.载单宁酸铁和紫杉醇相变型纳米粒用于体外超声显像及治疗视网膜母细胞瘤[J].中国医学影像技术,2020,36(6):801~807
载单宁酸铁和紫杉醇相变型纳米粒用于体外超声显像及治疗视网膜母细胞瘤
Phase-changeable nanoparticles loaded with Fe-tannic acid/paclitaxel for in vitro ultrasound imaging and treatment of retinoblastoma
投稿时间:2019-12-13  修订日期:2020-04-08
DOI:10.13929/j.issn.1003-3289.2020.06.001
中文关键词:  视网膜母细胞瘤  超声检查  分子成像  纳米微粒
英文关键词:retinoblastoma  ultrasonography  molecular imaging  nanoparticles
基金项目:重庆市科学技术委员会基础与前沿项目(cstc2018jcyjAX0562)。
作者单位E-mail
袁勋 重庆医科大学附属第二医院眼科, 重庆 400010
重庆医科大学超声分子影像重庆市重点实验室, 重庆 400010 
 
鞠丰翼 重庆医科大学附属第二医院眼科, 重庆 400010
重庆明达眼科医院眼科, 重庆 400010 
 
张玙 重庆明达眼科医院眼科, 重庆 400010  
乔斌 重庆医科大学超声分子影像重庆市重点实验室, 重庆 400010  
王志刚 重庆医科大学超声分子影像重庆市重点实验室, 重庆 400010  
杜之渝 重庆医科大学附属第二医院眼科, 重庆 400010 dr.duzhiyu@163.com 
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中文摘要:
      目的 制备可用于早期诊断和治疗视网膜母细胞瘤(Rb)的纳米粒,体外评价其超声显像和治疗效果。方法 制备载单宁酸铁(FeTA)和紫杉醇(PTX)并包裹全氟戊烷(PFP)的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒,检测其粒径、电位、电镜、吸光度、包封率、载药量等相关表征,评估808激光(1 W/cm2,5 min)辐照前后温度变化和超声信号改变,光镜下观察纳米粒相变情况。体外检测FeTA/PLGA/PFP纳米粒的生物安全性。设立空白对照组、激光组、FeTA/PLGA/PTX/PFP(FPTP)组、FeTA/PLGA/PTX/PFP+激光(FPTP+激光)组及不同浓度(0、0.250、0.500、1.000 g/L)FPTP+激光组,检测激光辐照5 min后各纳米粒组对肿瘤细胞的杀伤效果。结果 成功制备出FeTA/PLGA/PTX/PFP纳米粒,粒径(155.8±55.68)nm,电位(-27.3±5.14)mV,透射电子显微镜下见黑色FeTA外壳包裹核心灰白球形结构,PTX包封率(70.89±8.03)%,载药率(9.61±0.63)%。体外激光辐照FPTP纳米粒后温度上升与浓度呈正相关,B模式和造影模式超声信号也随浓度增加而增强。FPTP+激光组对Y79细胞的杀伤作用比空白对照组、激光组、FPTP组更强,并随浓度增加而增强。结论 成功制备出载单宁酸铁和紫杉醇的相变型纳米粒,具有良好的光热效应和超声显像效果,对Y79细胞有强杀伤作用,有望用于Rb实现诊疗一体。
英文摘要:
      Objective To prepare nanoparticles able to be used in early diagnosis and treatment of retinoblastoma (Rb), and to evaluate the in vitro ultrasound imaging capability and photothermal effect. Methods Nanoparticles containing poly(lactic-co-glycolic acid) (PLGA) shell, Fe-tannic acid (FeTA), paclitaxel (PTX) and perflenapent (PFP) were prepared by double emulsification. The particle size, potential, encapsulation efficiency and drug loading rate were measured. The temperature and ultrasound signal change were evaluated after 808 nm near-infrared laser (1 W/cm2, 5 min) irradiation, and the phase transition of nanoparticles was observed under light microscope. Moreover, the biosafety of FeTA/PLGA/PFP nanoparticles was assessed in vitro. The following experimental groups were established according to different types of nanoparticles, i.e. control group, laser group, FeTA/PLGA/PTX/PFP (FPTP) group, FeTA/PLGA/PTX/PFP+laser (FPTP+laser) group as well as different concentrations of nanoparticles (0, 0.250, 0.500, 1.000 g/L) in FPTP+laser group. The killing effects on Y79 cells in all aforementioned groups were evaluated after irradiation for 5 minutes. Results FeTA/PLGA/PTX/PFP nanoparticles were successfully prepared, the average particle size of nanoparticles was (155.8±55.68) nm and the mean surface charge was (-27.3±5.14) mV. Gray core with black FeTA coated nanoparticles could be seen under transmission electron microscope. The encapsulation efficiency and drug loading rate of particles was (70.89±8.03)% and (9.61±0.63)%, respectively. In addition, temperature increased when applying irradiation in vitro and positively correlated with the concentration of nanoparticles. Moreover, the ultrasonic signals in B-mode and imaging-mode enhanced with increasing concentration of nanoparticles. The killing effect against Y79 in FPTP+laser group was stronger than that of control group, laser group and FTTP group in vitro, positively correlated with the concentration of nanoparticles. Conclusion The phase changeable nanoparticles loaded with Fe-tannic acid and PFP were successfully prepared and possessed excellent photothermal effect and ultrasound imaging effect along with a robust killing effect on Y79 cells, being expected to realize the integrated approach in diagnosis and treatment of Rb.
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