Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai, China.
Clinical Laboratory, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
J Cell Biochem. 2019 Nov;120(11):18650-18658. doi: 10.1002/jcb.28950. Epub 2019 Jul 24.
This study aims to explore the ability of magnetic resonance imaging (MRI) in mucin 1 (MUC1) modified superparamagnetic iron oxide nanoparticle (SPION) targeting human pancreatic cancer (PC). The MUC1 target-directed probe was prepared through MUC1 conjugated to SPION using the chemical method to assess its physiochemical characteristics, including hydration diameter, surface charge, and magnetic resonance signal. The cytotoxicity of MUC1-USPION was verified by MTS assay. BxPC-3 was cultured with MUC1-USPION and SPION in different concentrations. The combined condition of the targeted probes and cells were observed through Prussian blue staining. The nude mice model of pancreatic cancer was established to investigate the application of the probe. MRI was performed to determine the intensity of the signal of the transplanted tumor, while immunohistochemistry and Western blot analysis were performed to detect the expression of MUC1 after taking the transplanted tumor specimen. The particle size of the prepared molecular probe was 63.5 ± 3.2 nm, and the surface charge was 10.2 mV. Furthermore, the probe solution could significantly reduce the MRI at T , and the magnetic resonance transverse relaxation rate (ΔR ) has a linear relationship with the concentration of iron in the solution. The cell viability of MUC1-USPION in different concentrations revealed no statistical difference, according to the MTS assay. In vitro, the MRI demonstrated decreased T2WI signal intensity in both groups, especially the targeting group. In vivo, MUC1 could selectively accumulate in the nude mice model, and significantly reduce the T signal strength. In subsequent experiments, the expression of MUC1 was high in pancreatic cancer tissues, but low in normal pancreatic tissues, as determined by immunohistochemistry and Western blot analysis. The prepared samples can be combined with pancreatic cancer tissue specificity by in vivo imaging, providing reliable early in vivo imaging data for disease diagnosis.
本研究旨在探讨磁共振成像（MRI）在粘蛋白 1（MUC1）修饰的超顺磁性氧化铁纳米粒子（SPION）靶向人胰腺癌（PC）中的能力。通过化学方法将 MUC1 与 SPION 连接，制备 MUC1 靶向探针，评估其理化特性，包括水合粒径、表面电荷和磁共振信号。通过 MTS 测定法验证 MUC1-USPION 的细胞毒性。在不同浓度下，用 MUC1-USPION 和 SPION 培养 BxPC-3。通过普鲁士蓝染色观察靶向探针和细胞的联合情况。建立胰腺癌裸鼠模型，研究探针的应用。进行 MRI 以确定移植瘤信号强度，同时进行免疫组织化学和 Western blot 分析，检测移植瘤标本中 MUC1 的表达。制备的分子探针的粒径为 63.5±3.2nm，表面电荷为 10.2mV。此外，探针溶液可显著降低 T 的 MRI，磁共振横向弛豫率（ΔR）与溶液中铁浓度呈线性关系。不同浓度的 MUC1-USPION 的细胞活力根据 MTS 测定法没有统计学差异。体外，MRI 显示两组 T2WI 信号强度均降低，尤其是靶向组。体内，MUC1 可选择性地在裸鼠模型中聚集，并显著降低 T 信号强度。在后续实验中，免疫组织化学和 Western blot 分析表明，MUC1 在胰腺癌组织中高表达，而在正常胰腺组织中低表达。制备的样品可通过体内成像与胰腺癌组织特异性结合，为疾病诊断提供可靠的早期体内成像数据。
