孕激素受体靶向聚乳酸-羟基乙酸-超顺磁性氧化铁分子探针的制备及其性能  

Preparation of PR-SPIO-PLGA molecular probe and its property

作　　者：章娉[1] 周佳[1] 唐焱[1] 刘红雨[1] ZHANG Ping;ZHOU Jia;TANG Yan;LIU Hongyu(Department of Ultrasound Diagnosis,First Affiliated Hospital,University of South China,Hengyang 421001,China)

机构地区：[1]南华大学附属第一医院超声科,湖南衡阳421001

出　　处：《吉林大学学报（医学版）》2018年第6期1307-1311,共5页Journal of Jilin University：Medicine Edition

基　　金：湖南省教育厅科学研究重点项目资助课题(14A126);湖南省衡阳市科技局科研基金资助课题(2016KJ37)

摘　　要：目的:探讨载孕激素受体(PR)靶向聚乳酸-羟基乙酸(PLGA)-超顺磁性氧化铁(SPIO)及全氟己烷(PFP)分子探针(PR-s-PFP/PLGA)的构建方法及其对乳腺癌细胞体外靶向结合的可行性。方法:制备s-PFP/PLGA纳米颗粒,检测s-PFP/PLGA纳米颗粒的直径和平均电位。细胞毒性实验不同浓度s-PFP/PLGA条件下检测各组细胞相对增殖率(RGR)。观察不同浓度s-PFP/PLGA纳米颗粒的体外磁共振成像(MRI)、体外光声成像和体外超声成像,高强度聚焦超声(HIFU)检测s-PFP/PLGA纳米颗粒辐照后回声强度值。采用碳二亚胺法制备PR-s-PFP/PLGA探针,体外培养高表达PR的乳腺癌细胞株T-47d,将DiO绿色荧光标记的T-47d细胞分为靶向显像剂组、非靶向组和空白对照组,观察探针与各组细胞的结合情况。结果:透射电镜下s-PFP/PLGA呈球形,SPIO颗粒均匀分布在外壳上,平均粒径为(738.5±181.2)nm,平均电位为(-15.8±5.7)mV,并检测到明显光声信号。体外超声显像中s-PFP/PLGA纳米颗粒呈点状高回声,HIFU辐照后其回声强度值增大。s-PFP/PLGA纳米颗粒在T1加权图像上的信号得到增强。在激光扫描共聚焦显微镜下,靶向显像剂组被T-47d细胞吞噬的s-PFP/PLGA纳米颗粒发出红色荧光。结论:PR-SPIO-PLGA具有优良的理化性质及稳定性,生物安全性好,肿瘤靶向结合能力强。Objective:To explore the method to construct the progesterone receptor(PR)-superparamagnetic iron oxide(SPIO)-poly 1actic-co-glycolic acid(PLGA)and perfluorohexane(PFP)molecular probe(PR-s-PFP/PLGA),and to investigate its targeted possibility of binding the breast cancer cells in vitro.Methods:The s-PFP/PLGA nanoparticles were prepared and the diameter and average potential of s-PFP/PLGA nanoparticles were detected.Cytotoxicity experiment was used to compare the relative proliferation rates(RGR)of cells with different concentrations of s-PFP/PLGA.The magnetic resonance imaging(MRI),photoacoustic imaging(PAI)and ultrasound imaging of s-PFP/PLGA nanoparticles were detected,and the echo intensity of s-PFP/PLGA nanoparticles was observed by high intensity focused ultrasound(HIFU)in vitro.The PR-s-PFP/PLGA probe was prepared by carbodiimide method.The breast cancer cell line T-47d with high expression of PR was cultured in vitro.The T-47d cells with DiO green fluorescence were divided into targeted imaging agent group,non-targeted group and blank control group.The binding of the probe to the cells in various groups was observed.Results:The s-PFP/PLGA nanoparticles were spherical under transmission electron microscope(TEM).The SPIO particles were evenly distributed on the shell,the average particle size was(738.5±181.2)nm and the average potential was(-15.8±5.7)mV,and the obvious photoacoustic signals were found.The ultrasound imaging of s-PFP/PLGA nanoparticles in vitro showed a punctate high-level echo,and the echo intensity was enhanced after HIFU irradiation.With the increasing of iron concentrations,the MRI signals showed a increasing trend in T1W1.Under laser scanning confocal microscope,the s-PFP/PLGA nanoparticles,which was phagocytized by T-47d cells,emitted red fluorescence.Conclusion:PR-SPIO-PLGA has excellent physicochemical properties,good stability and strong targeting effect on the cancer cells.

关 键 词：超声检查 造影剂 磁共振成像 顺磁性氧化铁 全氟己烷 

分 类 号：Q691.2[生物学—生物物理学] R737.9[医药卫生—肿瘤]