Department of Chemistry, Jagiellonian University, Kraków, Poland.
Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland.
Int J Nanomedicine. 2021 Sep 24;16:6537-6552. doi: 10.2147/IJN.S324354. eCollection 2021.
Epithelial-mesenchymal (EMT) transition plays an important role in metastasis and is accompanied by an upregulation of N-cadherin expression. A new nanoparticulate system (SPION/CCh/N-cad) based on superparamagnetic iron oxide nanoparticles, stabilized with a cationic derivative of chitosan and surface-modified with anti-N-cadherin antibody, was synthetized for the effective capture of N-cadherin expressing circulating tumor cells (CTC).
The morphology, physicochemical, and magnetic properties of the system were evaluated using dynamic light scattering (DLS), fluorescence spectroscopy, Mössbauer spectroscopy, magnetometry, and fluorescence spectroscopy. Atomic force microscopy (AFM), confocal microscopy and flow cytometry were used to study the interaction of our nanoparticulate system with N-cadherin expressed in prostate cancer cell lines (PC-3 and DU 145). A purpose-built cuvette was used in the cancer cell capture experiments.
The obtained nanoparticles were a spherical, stable colloid, and exhibited excellent magnetic properties. Biological experiments confirmed that the novel SPION/CCh/N-cad system interacts specifically with N-cadherin present on the cell surface. Preliminary studies on the magnetic capture of PC-3 cells using the obtained nanoparticles were successful. Incubation times as short as 1 minute were sufficient for the synthesized system to effectively bind to the PC-3 cells.
Results obtained for our system suggest a possibility of using it to capture CTC in the flow conditions.
上皮-间充质(EMT)转化在转移中起着重要作用,并伴随着 N-钙黏蛋白表达的上调。一种新型的基于超顺磁性氧化铁纳米粒子的纳米颗粒系统(SPION/CCh/N-cad),由壳聚糖的阳离子衍生物稳定,并通过抗 N-钙黏蛋白抗体表面修饰,用于有效捕获表达 N-钙黏蛋白的循环肿瘤细胞(CTC)。
使用动态光散射(DLS)、荧光光谱、穆斯堡尔光谱、磁强计和荧光光谱评估系统的形态、物理化学和磁性能。原子力显微镜(AFM)、共聚焦显微镜和流式细胞术用于研究我们的纳米颗粒系统与前列腺癌细胞系(PC-3 和 DU 145)中表达的 N-钙黏蛋白的相互作用。在癌细胞捕获实验中使用了专门设计的比色杯。
获得的纳米粒子呈球形、稳定的胶体,表现出优异的磁性能。生物学实验证实,新型 SPION/CCh/N-cad 系统与细胞表面存在的 N-钙黏蛋白特异性相互作用。使用获得的纳米粒子对 PC-3 细胞进行磁性捕获的初步研究取得了成功。合成系统与 PC-3 细胞有效结合所需的孵育时间短至 1 分钟。
我们的系统的研究结果表明,有可能在流动条件下使用它来捕获 CTC。