王中领,唐纳,王悍,解学乾,张在先,张贵祥.制备anti-EGFR-PEG-SPIO靶向纳米分子探针对肺腺癌细胞行体外靶向MR成像[J].中国医学影像技术,2017,33(12):1797~1801 |
制备anti-EGFR-PEG-SPIO靶向纳米分子探针对肺腺癌细胞行体外靶向MR成像 |
Preparation of anti-EGFR-PEG-SPIO molecular probe and its targeting MRI for lung adenocarcinoma cells |
投稿时间:2016-12-06 修订日期:2017-10-10 |
DOI:10.13929/j.1003-3289.201612019 |
中文关键词: 靶向成像 肺 腺癌 分子探针 超顺磁性氧化铁 |
英文关键词:Targeting imaging Lung Adenocarcinoma Molecular probe Superparamagnetic iron oxide-dopamine |
基金项目:国家自然科学基金(81371623)。 |
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中文摘要: |
目的 探讨anti-EGFR-PEG-SPIO纳米分子探针对表皮生长因子受体(EGFR)高表达肺腺癌细胞的靶向性及利用MRI对其监测的可行性。方法 制备anti-EGFR靶向纳米分子探针(anti-EGFR-PEG-SPIO)及非靶向纳米分子探针(PEG-SPIO),行电镜(TEM)观察,并测量水合粒径及弛豫率等表征。之后将不同Fe浓度(0、10、20、40、60、80 μg/ml)的anti-EGFR-PEG-SPIO和PEG-SPIO分别与H460细胞孵育2 h后,进行体外MR成像,观察其T2WI信号强度及信号强度变化率。行H460细胞普鲁士蓝染色和电镜观察细胞摄取Fe情况。结果 不同Fe浓度anti-EGFR-PEG-SPIO及PEG-SPIO探针分别与H460细胞孵育2 h后,前者显示H460细胞的信号强度随Fe浓度的升高而明显减低,Fe浓度为60 μg/ml时,相对于0、10、20、40、80 μg/ml,信号强度变化率约为-58.2%、-82.7%、-94.4%和-98.3%;而后者显示H460细胞信号强度减低相对不明显。普鲁士蓝染色及TEM结果显示anti-EGFR-PEG-SPIO的H460细胞内可见大量铁颗粒沉积,而PEG-SPIO的肿瘤细胞内仅可见少量铁颗粒沉积。结论 自行制备的anti-EGFR-PEG-SPIO分子探针对H460肺腺癌细胞具有靶向效应,采用3.0T MR扫描仪可对其进行监测。 |
英文摘要: |
Objective To observe the targeting function of high affinity anti-EGFR monoclonal antibody (Cetuximab)-conjugated superparamagnetic iron oxide-dopamine (anti-EGFR-PEG-SPIO) lung cancer cells via epidermal growth factor receptor (EGFR), as well as the feasibility for surveillance of tumor targeting with MRI. Methods Nanoparticles (NPs) of anti-EGFR-PEG-SPIO and PEG-SPIO were prepared, and the morphology of nanoparticles was observed with transmission electron microscope (TEM). The hydrodynamic diameter and R2 values of nanoparticles before and after conjugation with anti-EGFR were performed with dynamic light scattering (DLS) and MRI. MRI was performed in incubation with anti-EGFR-PEG-SPIO and PEG-SPIO after 2 h in vitro. The cellular uptake of anti-EGFR-PEG-SPIO and PEG-SPIO was further evaluated using Prussian blue staining and TEM. Results Anti-EGFR-PEG-SPIO and PEG-SPIO showed signal intensity of H460 cells on T2WI, decreased significantly compared with PEG-SPIO. The rate of signal intensity change was -58.2%, -82.7%, -94.4% and -98.3%, respectively, at iron concentrations of (0, 10, 20, 40, 80 μg/ml) of anti-EGFR-PEG-SPIO. Prussian blue staining and TEM showed that a lot of intracellular irons of anti-EGFR-PEG-SPIO were observed in H460 cells, but few of PEG-SPIO. Conclusion The effect of active targeting via anti-EGFR in EGFR overexpressed cells can be achieved with anti-EGFR-PEG-SPIO in H460 cells in vitro, and the targeting delivery process could be monitored with 3.0T MRI. |
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