摘要
目的制备精氨酸-甘氨酸-天冬氨酸环肽(c RGD肽)修饰的聚乙二醇-聚乳酸-羟基乙酸(PEG-PLGA)高分子聚合物靶向纳米造影剂c RGD-PEG-PLGA@PFPNPs(c RGD-NPs),探究其表征、相变及对小鼠乳腺癌细胞(4T1)的靶向性及超声成像。材料与方法利用双乳化法制成c RGD-NPs,验证c RGD与PEG-PLGA连接情况,观察cRGD-NPs表征、热致相变稳定性等基本特征;检测其对4T1细胞活性的影响;使用激光共聚焦显微镜,将BALB/c小鼠分为靶向组3只及非靶向组3只,通过活体成像观察小鼠体内外乳腺癌细胞摄取c RGD-NPs情况;观察c RGD-NPs声致相变及造影效果。结果成功制备c RGD-NPs,光镜与透射电镜下均表现为形态规则、大小均一的球形,平均粒径为(93.19±31.41)nm;不同浓度c RGD-NPs同4T1细胞共孵育不同时间后,细胞活力均>85%。激光共聚焦显微镜及活体组织荧光成像观察显示,与非靶向纳米粒组相比,c RGD-NPs组更多聚集于肿瘤细胞周围。随着低强度聚焦超声辐照时间推移增加,体外超声造影成像效果越好,在相同条件下也实现了体内乳腺肿瘤显影。结论cRGD-NPs是一种可靶向聚集于4T1细胞区域,具有靶向定位释药潜能且可显影的纳米级载体,可为临床乳腺癌化疗及靶向治疗提供新思路。
Purpose To prepare PEG-PLGA targeted nanoparticle contrast agent c RGD-PEG-PLGA@PFP NPs(c RGD-NPs),and observe its characterization,active targeting ability for mouse breast cancer cells(4T1 cells)and imaging effect.Materials and Methods c RGD-NPs were prepared by the double emulsification method.The connection of cRGD and PEG-PLGA,characterization and morphology of NPs were detected and observed.The safety of nanoparticles was detected.Confocal laser microscopy and in vivo imaging in mouse(3 in targeted group,3 in non-targeted group)were used to observe the uptake of targeted nanoparticles in breast cancer cells.The phase transformation and contrast imaging effect of nanoparticles were observed.Results c RGD-NPs was successfully prepared.Under optical microscope and transmission electron microscope,cRGD-NPs showed regular spherical shape and uniform size,with an average particle size of(93.19±31.41)nm.The cell viability of 4T1 cells were all>85%after co-incubation with different concentrations of nanoparticles for different time.Confocal laser microscopy and fluorescence imaging in vivo showed that cRGD-NPs clustered around tumor cells more than those in the non-targeted labeling group.With the increase of low-intensity focused ultrasound irradiation time,the imaging effect of contrast-enhanced ultrasound in vitro was enhanced,and the CEUS imaging of breast tumors in vivo was also achieved under the same conditions.Conclusion c RGD-PEG-PLGA@PFP NPs is a nanoscale carrier that can not only target the 4T1 breast cell region actively,but also realize CEUS imaging,and has potential of targeted drug release,which provides a new idea for clinical breast cancer chemotherapy and targeted therapy.
作者
申洪远
陶宏宇
张芙蓉
王晨雨
米成嵘
SHEN Hongyuan;TAO Hongyu;ZHANG Furong;WANG Chenyu;MI Chengrong(Department of Ultrasound,Ningxia Medical University,Yinchuan 750004,China;不详)
出处
《中国医学影像学杂志》
CSCD
北大核心
2022年第5期423-429,共7页
Chinese Journal of Medical Imaging
基金
国家自然科学基金项目(81960317)。
