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Promoting Multivalent Antibody–Antigen Interactions by Tethering Antibody Molecules on a PEGylated Dendrimer-Supported Lipid Bilayer
Biomacromolecules ( IF 6.2 ) Pub Date : 2018-01-11 00:00:00 , DOI: 10.1021/acs.biomac.7b01515
Po-Ying Yeh,Yih-Ruey Chen,Chien-Fang Wang,Ying-Chih Chang

To efficiently isolate maximal quantity of circulating tumor cells (CTCs) and circulating tumor cell microembolis (CTMs) from patient blood by antibody coated microfluidics, a multifunctional, pegylated polyamidoamine-dendrimers conjugated supported lipid bilayer surface construct was proposed to enhance accessibility of antibody molecules to the antigen molecules on target CTCs. The combination of a hydrated, stretchable dendrimer and a laterally mobile supported lipid bilayer (SLB) provide attached antibody molecules with 2.5-dimensional chain movement, achieving multivalency between the surface antibody and cell antigen molecules. An over 170% enhancement is distinctive for Panc-1 cells that expresses low antigen level. Of seven pancreatic ductal adenocarcinoma patients, an average 440 single CTCs and 90 CTMs were collected in 2 mL of peripheral blood, which were 1.6 times and 2.3 times more, than those captured by the SLB-only microfluidics. In summary, we have demonstrated a material design to enhance multivalent antibody–antigen interaction, which is useful for rare cell enrichment and cancer detection.

中文翻译:

通过在聚乙二醇化的树状大分子支持的脂质双层上束缚抗体分子来促进多价抗体-抗原相互作用。

为了通过抗体包被的微流体有效地从患者血液中分离出最大数量的循环肿瘤细胞(CTC)和循环肿瘤细胞微栓塞(CTM),提出了一种多功能的聚乙二醇化聚酰胺酰胺-树状聚合物共轭支持的脂质双层表面构建体,以增强抗体分子对目标CTC上的抗原分子。水合的,可拉伸的树状大分子和可横向移动的脂质双分子层(SLB)的结合为附着的抗体分子提供了2.5维链运动,从而在表面抗体和细胞抗原分子之间实现了多价。对于表达低抗原水平的Panc-1细胞,超过170%的增强是独特的。在7例胰腺导管腺癌患者中,在2 mL的外周血中平均收集到440个单CTC和90个CTM,这比仅使用SLB的微流体所捕获的多1.6倍和2.3倍。总而言之,我们已经展示了一种增强多价抗体-抗原相互作用的材料设计,可用于稀有细胞富集和癌症检测。
更新日期:2018-01-11
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