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

doi:10.13481/j.1671-587x.20180634

摘要/Abstract

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。

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

Abstract: 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.

Key words: ultrasonography, contrast media, magnetic resonance imaging, super paramagnetic iron oxide, perfluorohexane

中图分类号:

Q691.2

章娉, 周佳, 唐焱, 刘红雨. 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[J]. 吉林大学学报(医学版), 2018, 44(06): 1307-1311.

ZHANG Ping, ZHOU Jia, TANG Yan, LIU Hongyu. Preparation of PR-SPIO-PLGA molecular probe and its property[J]. Journal of Jilin University(Medicine Edition), 2018, 44(06): 1307-1311.

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