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受生物启发的多功能适体功能化纳米界面工程用于增强循环肿瘤细胞的捕获和释放。

Bioinspired Engineering of a Multivalent Aptamer-Functionalized Nanointerface to Enhance the Capture and Release of Circulating Tumor Cells.

机构信息

Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, the Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.

出版信息

Angew Chem Int Ed Engl. 2019 Feb 18;58(8):2236-2240. doi: 10.1002/anie.201809337. Epub 2019 Jan 11.

DOI:10.1002/anie.201809337
PMID:30548959
Abstract

Circulating tumor cell (CTC)-enrichment by using aptamers has a number of advantages, but the issue of compromised binding affinities and stabilities in real samples hinders its wide applications. Inspired by the high efficiency of the prey mechanism of the octopus, we engineered a deterministic lateral displacement (DLD)-patterned microfluidic chip modified with multivalent aptamer-functionalized nanospheres (AP-Octopus-Chip) to enhance capture efficiency. The multivalent aptamer-antigen binding efficiency improves 100-fold and the capture efficiency is enhanced more than 300 % compared with a monovalent aptamer-modified chip. Moreover, the captured cancer cells can be released through a thiol exchange reaction with up to 80 % efficiency and 96 % viability, which is fully compatible with downstream mutation detection and CTC culture. Using the chip, we were able to find CTCs in all cancer samples analyzed.

摘要

基于适体的循环肿瘤细胞(CTC)富集具有许多优势,但在实际样本中结合亲和力和稳定性受损的问题阻碍了其广泛应用。受章鱼高效猎食机制的启发,我们设计了一种带有多价适体功能化纳米球的确定性侧向位移(DLD)图案微流控芯片(AP-Octopus-Chip),以提高捕获效率。与单价适体修饰的芯片相比,多价适体-抗原结合效率提高了 100 倍,捕获效率提高了 300%以上。此外,通过硫醇交换反应,捕获的癌细胞的释放效率可达 80%,存活率可达 96%,这与下游的突变检测和 CTC 培养完全兼容。使用该芯片,我们能够在分析的所有癌症样本中找到 CTC。

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