Specific capture and release of circulating tumor cells using aptamer-modified nanosubstrates.

Specific capture and release of circulating tumor cells using aptamer-modified nanosubstrates.
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DOI:
10.1002/adma.201300082
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发表时间:
2013-04-24
期刊:
影响因子:
29.4
通讯作者:
Fang, Xiaohong
Fang, Xiaohong
中科院分区:
材料科学1区
文献类型:
--
作者:
Shen, Qinglin;Xu, Li;Zhao, Libo;Wu, Dongxia;Fan, Yunshan;Zhou, Yiliang;OuYang, Wei-Han;Xu, Xiaochun;Zhang, Zhen;Song, Min;Lee, Tom;Garcia, Mitch A.;Xiong, Bin;Hou, Shuang;Tseng, Hsian-Rong;Fang, Xiaohong

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Circulating tumor cells (CTCs)[1] are cancer cells that have propagated from tumors, spreading into the bloodstream as the cellular origin of fatal metastasis. Besides conventional diagnostic approaches (eg, tumor biopsy, anatomical/molecular imaging and serum marker detection), detecting CTCs in peripheral blood is of prognostic value in different types of solid tumors, especially for predicting patient survival. The fact is that CTC detection have been technically challenging because of the extremely low abundance (a few to hundreds per mL) of CTCs among a high number (10 9 cells mL− 1) of hematologic cells.[2] Over the past decade, a diversity of diagnostic technologies has been demonstrated for CTC detection using different working mechanisms. The current FDA-cleared CellSearch Assay is based on immunomagnetic separation of CTCs. Due to its unsatisfactory efficiency and high cost, researchers have been exploiting new technologies [3](eg, flow cytometry, sizebased filtration systems, and microfluidic devices that may offer improved sensitivity and reduced cost for CTC detection). In addition to the prognostic utility of CTC-based diagnostics, it is conceivable that the molecular signatures and functional readouts derived from CTCs will shed much valuable insight into tumor biology during the critical window where therapeutic intervention could make a significant difference. Previously, we have demonstrated a highly efficient, inexpensive CTC assay capable of enriching, identifying and enumerating CTCs in whole-blood samples collected from prostate cancer patients. Firstly, we pioneered a unique concept of “NanoVelcro” cell-affinity substrates,[4] by which capture agent (anti-EpCAM)-coated silicon nanowire substrates (SiNWS) were utilized to immobilize CTCs in a stationary device setting. The general applicability of the NanoVelcro substrates is supported by our recent studies, where other types of nanostructured substrates (eg, electrochemically deposited conjugated polymer nanofeatures,[5] and horizontally packed TiO 2 nanofibers [6]) can also be deposited onto substrates, exhibiting enhanced affinity for CTC capturing. Furthermore, recent studies by other groups [7] also have confirmed the utility of SiNWS (grafted with immune cell-specific capture agents) for capturing subpopulations of immune cells. The uniqueness of our approach is the use of nanostructured substrates: there are enhanced local topographic interactions [8] between the anti-EpCAM-coated nanosubstrates and nanoscaled cellular surface components (eg, microvilli) on a CTC, which are analogous to the working principle of a velcro. Secondly, by integrating a NanoVelcro substrate with a polydimethylsiloxane (PDMS)-based chaotic mixer [9] that enhances contact frequency between flow-through CTCs and the substrate, further improved CTC capture efficiency has been achieved.[10] Although NanoVelcro devices allow efficient and reproducible enumeration of CTCs in clinical setting, one of the remaining challenges is to confer cell-release performance to the NanoVelcro devices. A diagnostic assay capable of highly effective capture and specific release of CTCs will pave the way for implementing subsequent molecular and functional analyses.[11]On the basis of our previously reported NanoVelcro Chips, we introduce a new-generation NanoVelcro Chip (Figure 1) that is capable of not only capturing non-small cell lung cancer (NSCLC) CTCs from blood with high efficiency, but also recovering the nanosubstrate-immobilized NSCLC CTCs upon treatment of a nuclease solution. To achieve such an inexpensive and sensitive CTC capture and recovery platform, we …
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影响因子: --
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