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基于肽功能化硅纳米线基底的胰腺癌循环肿瘤细胞捕获和生物释放。

Capture and biological release of circulating tumor cells in pancreatic cancer based on peptide-functionalized silicon nanowire substrate.

机构信息

Department of Oncology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,

Cancer Center, Renmin Hospital, Wuhan University, Wuhan, China,

出版信息

Int J Nanomedicine. 2018 Dec 24;14:205-214. doi: 10.2147/IJN.S187892. eCollection 2019.

Abstract

BACKGROUND

Efficient and precise circulating tumor cells' (CTCs) capture and release with minimal effect on cell viability for CTCs' analysis are general requirements of CTCs' detection device in clinical application. However, these two essential factors are difficult to be achieved simultaneously.

METHODS

In order to reach the aforementioned goal, we integrated multiple strategies and technologies of staggered herringbone structure, nanowires' substrate, peptides, enzymatic release, specific cell staining, and gene sequencing into microfluidic device and the sandwich structure peptide-silicon nanowires' substrate was termed as Pe-SiNWS.

RESULTS

The Pe-SiNWS demonstrated excellent capture efficiency (95.6%) and high release efficiency (92.6%). The good purity (28.5%) and cell viability (93.5%) of CTCs could be obtained through specific capture and biological release by using Pe-SiNWS. The good purity of CTCs facilitated precise and quick biological analysis, and five types of KRAS mutation were detected in 16 pancreatic cancer patients but not in healthy donors.

CONCLUSION

The results proved that the effective capture, minor damage release, and precise analysis of CTCs could be realized simultaneously by our novel strategy. The successful clinical application indicated that our work was anticipated to open up new opportunities for the design of CTC microfluidic device.

摘要

背景

高效、精确地捕获循环肿瘤细胞(CTCs),同时最大限度地减少对细胞活力的影响,这是临床应用中 CTC 检测设备的普遍要求。然而,这两个关键因素很难同时实现。

方法

为了达到上述目标,我们将交错齿形结构、纳米线基底、肽、酶释放、特定细胞染色和基因测序等多种策略和技术集成到微流控装置中,将夹心结构的肽-硅纳米线基底命名为 Pe-SiNWS。

结果

Pe-SiNWS 表现出优异的捕获效率(95.6%)和高释放效率(92.6%)。通过使用 Pe-SiNWS 进行特异性捕获和生物释放,可以获得高纯度(28.5%)和高细胞活力(93.5%)的 CTCs。高纯度的 CTCs 有助于精确快速的生物学分析,在 16 名胰腺癌患者中检测到了 5 种 KRAS 突变,而在健康供体中则没有检测到。

结论

结果表明,我们的新策略可以同时实现 CTC 的有效捕获、轻微损伤释放和精确分析。成功的临床应用表明,我们的工作有望为 CTC 微流控装置的设计开辟新的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9d8/6307685/697a0f17550e/ijn-14-205Fig1.jpg

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