Greatly Enhanced CTC Culture Enabled by Capturing CTC Heterogeneity Using a PEGylated PDMS-Titanium-Gold Electromicrofluidic Device with Glutathione-Controlled Gentle Cell Release.
Greatly Enhanced CTC Culture Enabled by Capturing CTC Heterogeneity Using a PEGylated PDMS-Titanium-Gold Electromicrofluidic Device with Glutathione-Controlled Gentle Cell Release.
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DOI：
10.1021/acsnano.2c05195
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发表时间：
2022-07-26
期刊：
影响因子：
17.1
通讯作者：
He, Xiaoming
中科院分区：
文献类型：
--
作者：
Kwizera, Elyahb A.;Ou, Wenquan;Lee, Sojeong;Stewart, Samantha;Shamul, James G.;Xu, Jiangsheng;Tait, Nancy;Tkaczuk, Katherine H. R.;He, Xiaoming
循环肿瘤细胞（CTC，癌症转移和不良癌症预后的根本原因）非常难以体外培养用于放大，这阻碍了它们在癌症研究/预后和患者特异性治疗开发中的应用。在本文中，我们报告了一种稳健的电微流控芯片，其不仅用于高效捕获具有高纯度的异质性（EpCAM+和CD 44+）CTC，而且还用于具有高效率和活力的CTC的谷胱甘肽控制的温和释放。这是通过在器件中的聚二甲基硅氧烷（PDMS）表面涂覆10 nm金层通过4 nm钛耦合层来实现的，以便于通过硫醇-金化学进行捕获抗体的PEG化和连接。令人惊讶的是，EpCAM+乳腺CTC的百分比可以低至约35%（平均约70%），这表明通常使用的仅用EpCAM捕获CTC的方法可能错过许多EpCAM-CTC。此外，可以培养CD 44 + CTC以有效地形成3D球状体用于放大。相比之下，单独用EpCAM捕获的CTC在体外增殖较差，与文献一致。通过捕获CTC异质性，CTC可以成功培养/扩大规模的IV期患者的百分比从约6.3%提高到68.8%。这些发现表明，仅用EpCAM捕获CTC的常规做法错过了CTC异质性，包括关键的CD 44 + CTC。本研究对异种CTC的获取和规模化应用、了解肿瘤转移规律、方便地通过微创液/血活检靶向肿瘤转移的个体化治疗具有重要意义。
The circulating tumor cells (CTCs, the root cause of cancer metastasis and poor cancer prognosis) are very difficult to culture for scaleup in vitro, which has hampered their use in cancer research/prognosis and patient-specific therapeutic development. Herein, we report a robust electro-microfluidic chip for not only efficient capture of heterogeneous (EpCAM+ and CD44+) CTCs with high purity, but also glutathione-controlled gentle release of the CTCs with high efficiency and viability. This is enabled by coating the polydimethylsiloxane (PDMS) surface in the device with a 10-nm gold layer through a 4-nm titanium coupling layer, for convenient PEGylation and linkage of capture antibodies via the thiol-gold chemistry. Surprisingly, the percentage of EpCAM+ mammary CTCs can be as low as ~35% (~70% on average), showing the commonly used approach of capturing CTCs with EpCAM alone may miss many EpCAM- CTCs. Furthermore, the CD44+ CTCs can be cultured to form 3D spheroids efficiently for scaleup. In contrast, the CTCs captured with EpCAM alone are poor in proliferation in vitro, consistent with the literature. By capturing the CTC heterogeneity, the percentage of stage IV patients whose CTCs can be successfully cultured/scaled up is improved from ~6.3% to 68.8%. These findings demonstrate the common practice of CTC capture with EpCAM alone misses the CTC heterogeneity including the critical CD44+ CTCs. This study may be valuable to the procurement and scaleup of heterogenous CTCs, to facilitate the understanding of cancer metastasis and the development of cancer metastasis-targeted personalized cancer therapies conveniently via the minimally invasive liquid/blood biopsy.
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影响因子：
5.6
作者：
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通讯作者：
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影响因子：
64.5
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影响因子：
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作者：
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通讯作者：
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影响因子：
2.8
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