Lin Run, Li Yuancheng, MacDonald Tobey, Wu Hui, Provenzale James, Peng Xingui, Huang Jing, Wang Liya, Wang Andrew Y, Yang Jianyong, Mao Hui
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Colloids Surf B Biointerfaces. 2017 Feb 1;150:261-270. doi: 10.1016/j.colsurfb.2016.10.026. Epub 2016 Oct 13.
Detecting circulating tumor cells (CTCs) with high sensitivity and specificity is critical to management of metastatic cancers. Although immuno-magnetic technology for in vitro detection of CTCs has shown promising potential for clinical applications, the biofouling effect, i.e., non-specific adhesion of biomolecules and non-cancerous cells in complex biological samples to the surface of a device/probe, can reduce the sensitivity and specificity of cell detection. Reported herein is the application of anti-biofouling polyethylene glycol-block-allyl glycidyl ether copolymer (PEG-b-AGE) coated iron oxide nanoparticles (IONPs) to improve the separation of targeted tumor cells from aqueous phase in an external magnetic field. PEG-b-AGE coated IONPs conjugated with transferrin (Tf) exhibited significant anti-biofouling properties against non-specific protein adsorption and off-target cell uptake, thus substantially enhancing the ability to target and separate transferrin receptor (TfR) over-expressed D556 medulloblastoma cells. Tf conjugated PEG-b-AGE coated IONPs exhibited a high capture rate of targeted tumor cells (D556 medulloblastoma cell) in cell media (58.7±6.4%) when separating 100 targeted tumor cells from 1×10 non-targeted cells and 41 targeted tumor cells from 100 D556 medulloblastoma cells spiked into 1mL blood. It is demonstrated that developed nanoparticle has higher efficiency in capturing targeted cells than widely used micron-sized particles (i.e., Dynabeads).
以高灵敏度和特异性检测循环肿瘤细胞（CTC）对于转移性癌症的管理至关重要。尽管用于体外检测CTC的免疫磁技术在临床应用中已显示出有前景的潜力，但生物污垢效应，即复杂生物样品中的生物分子和非癌细胞在设备/探针表面的非特异性粘附，会降低细胞检测的灵敏度和特异性。本文报道了抗生物污垢的聚乙二醇-嵌段-烯丙基缩水甘油醚共聚物（PEG-b-AGE）包覆的氧化铁纳米颗粒（IONP）在外部磁场中用于改善从水相中分离靶向肿瘤细胞的应用。与转铁蛋白（Tf）共轭的PEG-b-AGE包覆的IONP对非特异性蛋白质吸附和脱靶细胞摄取表现出显著的抗生物污垢特性，从而大大增强了靶向和分离过表达转铁蛋白受体（TfR）的D556髓母细胞瘤细胞的能力。当从1×10个非靶向细胞中分离100个靶向肿瘤细胞以及从掺入1mL血液中的100个D556髓母细胞瘤细胞中分离41个靶向肿瘤细胞时，Tf共轭的PEG-b-AGE包覆的IONP在细胞培养基中对靶向肿瘤细胞（D556髓母细胞瘤细胞）表现出高捕获率（58.7±6.4%）。结果表明，所开发的纳米颗粒在捕获靶向细胞方面比广泛使用的微米级颗粒（即Dynabeads）具有更高的效率。
