Biomaterials and Tissue Engineering Research Group, Department of Interdisciplinary Technologies, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran 15179-64311, Iran.
Department of Oncology, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran.
Anal Chem. 2024 Mar 19;96(11):4377-4384. doi: 10.1021/acs.analchem.3c03567. Epub 2024 Mar 5.
Low number of circulating tumor cells (CTCs) in the blood samples and time-consuming properties of the current CTC isolation methods for processing a small volume of blood are the biggest obstacles to CTC usage in practice. Therefore, we aimed to design a CTC dialysis system with the ability to process cancer patients' whole blood within a reasonable time. Two strategies were employed for developing this dialysis setup, including (i) synthesizing novel core-shell Cu ferrites consisting of the Cu-CuFeO core and the MIL-88A shell, which are targeted by the anti-HER2 antibody for the efficient targeting and trapping of CTCs; and (ii) fabricating a microfluidic system containing a three-dimensional (3D)-printed microchannel filter composed of a polycaprolactone/FeO nanoparticle composite with pore diameter less than 200 μm on which a high-voltage magnetic field is focused to enrich and isolate the magnetic nanoparticle-targeted CTCs from a large volume of blood. The system was assessed in different aspects including capturing the efficacy of the magnetic nanoparticles, CTC enrichment and isolation from large volumes of human blood, side effects on blood cells, and the viability of CTCs after isolation for further analysis. Under the optimized conditions, the CTC dialysis system exhibited more than 80% efficacy in the isolation of CTCs from blood samples. The isolated CTCs were viable and were able to proliferate. Moreover, the CTC dialysis system was safe and did not cause side effects on normal blood cells. Taken together, the designed CTC dialysis system can process a high volume of blood for efficient dual diagnostic and therapeutic purposes.
血液样本中循环肿瘤细胞 (CTC) 的数量较少,以及当前用于处理小体积血液的 CTC 分离方法耗时较长,这是 CTC 在实际应用中面临的最大障碍。因此,我们旨在设计一种 CTC 透析系统,使其能够在合理的时间内处理癌症患者的全血。为了开发这种透析设备,我们采用了两种策略,包括 (i) 合成新型核壳结构的 Cu 铁氧体,其由 Cu-CuFeO 核和 MIL-88A 壳组成,并用抗 HER2 抗体靶向,以实现 CTC 的高效靶向捕获;以及 (ii) 制造一种微流控系统,其中包含一个三维 (3D) 打印微通道过滤器,该过滤器由聚己内酯/FeO 纳米粒子复合材料组成,孔径小于 200μm,其上聚焦高电压磁场,从大量血液中富集和分离磁性纳米粒子靶向的 CTC。该系统在多个方面进行了评估,包括磁性纳米粒子的捕获效率、从大量人血中富集和分离 CTC、对血细胞的副作用以及分离后 CTC 的活力,以便进一步分析。在优化条件下,CTC 透析系统从血液样本中分离 CTC 的效率超过 80%。分离的 CTC 具有活力并能够增殖。此外,CTC 透析系统安全,不会对正常血细胞产生副作用。总之,设计的 CTC 透析系统可以处理大量血液,用于高效的双重诊断和治疗目的。
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