Self-propelled microrockets to capture and isolate circulating tumor cells.
Self-propelled microrockets to capture and isolate circulating tumor cells.
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自驱动微型火箭捕获和分离循环肿瘤细胞。
DOI：
10.1002/anie.201103189
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发表时间：
2011
影响因子：
--
通讯作者：
O. Farokhzad
中科院分区：
文献类型：
--
作者：
Weiwei Gao;O. Farokhzad
关于循环肿瘤细胞（CTC）的第一份报告可以追溯到1869年，当时澳大利亚医生托马斯·阿什沃思（Thomas Ashworth）在一名死于晚期转移性癌症的患者血液中观察到肿瘤细胞。从那时起，癌症研究已经证明了CTC在癌症转移扩散中发挥的关键作用。此外，CTC包含肿瘤基因型在癌症进展期间如何演变的关键信息。因此，可以从血液样本中产生更纯的CTC群体的技术是提供早期和非侵入性癌症检测沿着预测治疗反应和肿瘤进展的有力工具。尽管有这些重要性，但实际上，CTC非常罕见。从转移性肿瘤脱落的一些CTC与1 mL血液中约1000万个白细胞和50亿个红细胞混合，使其检测和分离成为一项艰巨的技术挑战。鉴于循环中CTC的相对缺乏，现有的CTC检测技术基于两个不同的步骤：从血液中富集CTC，然后确认纯化样品中的CTC。加强CTC富集或确认的方法是一个非常有前途的研究领域。CellSearch是迄今为止唯一获得FDA（美国食品和药物管理局）批准的检测方法，可用于检测乳腺癌、前列腺癌和结肠癌患者血液中的CTC。该测定基于从全血中免疫磁性分离上皮细胞粘附分子（EpCAM）阳性细胞，然后分析免疫染色的候选CTC。仍在开发中的AdnaTest是基于CTC的免疫磁性分离，然后进行多重实时聚合酶链反应（RT-PCR），用于定量肿瘤相关RNA转录物。后一种方法虽然理论上更敏感，但具有缺乏CTC的定量或形态信息的局限性;然而，它可以在CTC检测中起补充作用。纳米技术使各种越来越敏感和可重复的技术能够从血液样品中检测人类CTC。例如，已经开发了许多策略来基于CTC与循环红细胞和白细胞的可区分的物理性质（包括大小、密度、电荷、迁移性质和特定细胞类型相关的特征，例如黑素瘤细胞中的黑素细胞颗粒）分离CTC。与此同时，肿瘤相关抗原和免疫分离方法，流式细胞术或免疫磁性技术仍然是更明确的工具，以区分循环中的其他细胞的CTC。最近，已经开发了微流体通道内的EpCAM功能化微柱，以在精确控制的层流条件下捕获CTC，从而潜在地减少CTC损失和假阴性结果的数量。在最近的一期杂志中，由加州大学圣地亚哥分校（UCSD）的张良芳（Liangfang Zhang）和约瑟夫·王（Joseph Wang）领导的一个研究小组报告了一种捕获CTC的新方法。在他们的工作中，开发了一种自推进的“微型火箭”，当它通过细胞混合物导航时，可以选择性地拾取CTC，随后将捕获的细胞运送到所需的位置。纳米技术的最新进展见证了一些自推进货物运输平台。正如UCSD团队开发的微型火箭所示，它们可能为从复杂介质中简单，快速，有效地捕获和分离生物靶标提供许多机会。值得注意的是，UCSD团队开发的微火箭提供了一个新的例子，说明纳米技术如何将多种功能组装成纳米或微米级器件，随后可用于克服生物医学挑战。在这种情况下，它是能量线束，发电，运动控制和生物功能化的巧妙而复杂的组装，最终导致使用微火箭来分离CTC。由王，张和同事开发的微型火箭由一个卷起的金属片组成，由内而外有铂，铁和金。内部铂层将过氧化物转化为氧气和水。由于微型火箭的中空中心是锥形的，氧气泡仅通过一个开口排出，从而产生单向推进力。中铁层允许研究人员通过使用外部磁场来控制微型火箭。外部金层可以用靶向在结直肠癌、胃癌和胰腺癌中过表达的癌胚抗原（CEA）的抗体分子装饰。[*] W. Gao，Prof. Dr. O. C. Farokhzad纳米医学和生物材料实验室麻醉科，布莱根妇女医院哈佛医学院，75弗朗西斯街，波士顿，MA 02115（美国）电子邮件：ofarokhzad@zeus.bwh.harvard.edu亮点
The first report of circulating tumor cells (CTCs) can be traced back to 1869 when Thomas Ashworth, an Australian physician, observed tumor cells in the blood of a patient who succumbed to advanced metastatic cancer. Since then cancer research has proved the critical roles played by CTC in the metastatic spread of carcinomas. In addition, CTCs contain key information of how tumor genotypes evolve during the cancer progression. Therefore, technologies that can yield purer CTC populations from blood samples are powerful tools to provide early and noninvasive detection of cancer, along with the prediction of treatment responses and tumor progression. Despite these significances, in reality, CTCs are extremely rare. A few CTCs shed from metastatic tumors mingle with the approximately 10 million leukocytes and 5 billion erythrocytes in 1 mL of blood, making their detection and isolation a formidable technological challenge. Given the relative paucity of CTCs in circulation, the existing technologies for their detection are based on two distinct steps: the enrichment of the CTCs from blood followed by the confirmation of CTCs in the purified sample. Approaches to enhance the enrichment or confirmation of CTC are an extremely promising area of investigation. CellSearch is the only FDA (U.S. Food and Drug Administration)-approved assay up to date and it is available for detection of CTCs from the blood of patients with breast, prostate, and colon cancers. The assay is based on immunomagnetic separation of epithelial cell adhesion molecule (EpCAM) positive cells from whole blood followed by analysis of immunostained candidate CTCs. AdnaTest which is still under development is based on immunomagnetic separation of CTCs followed by multiplex real-time polymerase chain reaction (RT-PCR) for quantification of tumorassociated RNA transcripts. The latter approach while theoretically more sensitive has the limitation of lacking quantitative or morphological information of CTCs; however, it may serve a complementary role in CTC detections. Nanotechnology has enabled a variety of increasingly sensitive and reproducible techniques to detect human CTCs from blood samples. For example, a number of strategies have been developed to isolate CTCs based on their distinguishable physical properties from circulating erythrocytes and leukocytes including size, density, charge, migratory properties, and specific cell-type-related characteristics such as melanocytic granules in melanoma cells. Meanwhile, tumor-associated antigens and immunoseparation methods by flow cytometery or immunomagnetic techniques remain the more definitive tool to discriminate CTCs from other cells in circulation. More recently, EpCAM-functionalized microposts within microfluidic channels have been developed to capture CTC under precisely controlled laminar flow conditions to potentially decrease the number of CTC loss and false negative results. In a recent issue, a team of researchers led by Liangfang Zhang and Joseph Wang at the University of California, San Diego (UCSD) reported a novel approach to capture CTCs. In their work, a self-propelled “microrocket” was developed to selectively pick up CTCs as it navigated through a cell mixture and subsequently transported the captured cells to desired locations. Recent advances in nanotechnology have witnessed a number of self-propelled cargo transport platforms. As illustrated by the microrocket developed by the UCSD team, they are likely to open many opportunities for simple, fast, and effective capture and isolation of biological targets from complex medium. Markedly, the microrocket developed by the UCSD team offers a new example of how nanotechnology enables the assembly of multiple functionalities into nanoor microscale devices, which can be subsequently applied to overcome biomedical challenges. In this case, it is the clever and intricate assembly of energy harness, power generation, motion control, and biological functionalization that eventually leads to the use of microrockets to isolate CTCs. The microrocket developed by Wang, Zhang, and coworkers consists of a rolled-up metal sheet with platinum, iron, and gold from the inside out. The inner platinum layer converts peroxide to oxygen and water. As the hollow center of the microrocket is tapered, the oxygen bubbles vent only through one opening and thus produce a unidirectional propelling force. The mid iron layer allows researchers to steer the microrocket by using an external magnetic field. The outer gold layer can be decorated with antibody molecules that target carcinoembryonic antigen (CEA) over-expressed in colorectal, gastric, and pancreatic cancers. The specificity of [*] W. Gao, Prof. Dr. O. C. Farokhzad Laboratory of Nanomedicine and Biomaterials Department of Anesthesiology, Brigham and Women’s Hospital Harvard Medical School, 75 Francis Street, Boston, MA 02115 (USA) E-mail: ofarokhzad@zeus.bwh.harvard.edu Highlights
影响因子：
16.6
作者：
Balasubramanian, Shankar;Kagan, Daniel;Hu, Che-Ming Jack;Campuzano, Susana;Lobo-Castanon, M. Jesus;Lim, Nicole;Kang, Dae Y.;Zimmerman, Maria;Zhang, Liangfang;Wang, Joseph
通讯作者：
Wang, Joseph
DOI：
10.1056/nejmoa0800668
发表时间：
2008-07-24
期刊：
The New England journal of medicine
影响因子：
--
作者：
Maheswaran S;Sequist LV;Nagrath S;Ulkus L;Brannigan B;Collura CV;Inserra E;Diederichs S;Iafrate AJ;Bell DW;Digumarthy S;Muzikansky A;Irimia D;Settleman J;Tompkins RG;Lynch TJ;Toner M;Haber DA
通讯作者：
Haber DA
影响因子：
4.9
作者：
Gao W;Chan JM;Farokhzad OC
通讯作者：
Farokhzad OC