Doswald Simon, Herzog Antoine F, Zeltner Martin, Zabel Anja, Pregernig Andreas, Schläpfer Martin, Siebenhüner Alexander, Stark Wendelin J, Beck-Schimmer Beatrice
Institute of Chemical Engineering, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.
Institute of Anaesthesiology, University Hospital Zurich and University of Zurich, 8091 Zurich, Switzerland.
Pharmaceutics. 2022 Jul 1;14(7):1397. doi: 10.3390/pharmaceutics14071397.
The count of circulating tumor cells (CTCs) has been associated with a worse prognosis in different types of cancer. Perioperatively, CTCs detach due to mechanical forces. Diagnostic tools exist to detect and isolate CTCs, but no therapeutic technique is currently available to remove CTCs in vivo from unprocessed blood. The aim of this study was to design and test new magnetic nanoparticles to purify whole blood from CTCs. Novel magnetic carbon-coated cobalt (C/Co) nanoparticles conjugated with anti-epithelial cell adhesion molecule (EpCAM) antibodies were synthesized, and their antifouling and separation properties were determined. The newly developed C/Co nanoparticles showed excellent separation and antifouling properties. They efficiently removed tumor cells that were added to healthy subjects' blood samples, through an anti-EpCAM antibody interaction. The nanoparticles did not interact with other blood components, such as lymphocytes or the coagulation system. In blood samples of carcinoma patients suffering from metastatic disease, on average, ≥68% of CTCs were removed. These nanoparticles could prompt the development of a blood purification technology, such as a dialysis-like device, to perioperatively remove CTCs from the blood of cancer patients in vivo and potentially improve their prognosis.
循环肿瘤细胞(CTC)计数与不同类型癌症的预后较差相关。在围手术期,CTC会因机械力而脱离。现有的诊断工具可用于检测和分离CTC,但目前尚无治疗技术可在体内从未经处理的血液中去除CTC。本研究的目的是设计并测试新型磁性纳米颗粒,以从全血中纯化CTC。合成了与抗上皮细胞粘附分子(EpCAM)抗体偶联的新型磁性碳包覆钴(C/Co)纳米颗粒,并测定了它们的抗污和分离性能。新开发的C/Co纳米颗粒表现出优异的分离和抗污性能。它们通过抗EpCAM抗体相互作用,有效地去除了添加到健康受试者血液样本中的肿瘤细胞。纳米颗粒不与其他血液成分相互作用,如淋巴细胞或凝血系统。在患有转移性疾病的癌症患者的血液样本中,平均≥68%的CTC被去除。这些纳米颗粒可能会推动血液净化技术的发展,如类似透析的装置,以便在围手术期从癌症患者体内的血液中去除CTC,并有可能改善他们的预后。