The First Affiliated Hospital of Sun Yat-Sen University, State Key Laboratory of Optoelectronic Materials and Technologies, School of Electronics and Information Technology , Sun Yat-Sen University , Guangzhou 510006 , China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Sun Yat-sen University Cancer Center , Guangzhou 510060 , China.
Nano Lett. 2019 Oct 9;19(10):7201-7209. doi: 10.1021/acs.nanolett.9b02790. Epub 2019 Sep 30.
Downstream analysis of circulating tumor cells (CTCs) has provided new insights into cancer research. In particular, the detection of CTCs, followed by the regulation and monitoring of their intracellular activities, can provide valuable information for comprehensively understanding cancer pathogenesis and progression. However, current CTC detection techniques are rarely capable of regulation and monitoring of the intracellular microenvironments of cancer cells over time. Here, we developed a multifunctional branched nanostraw (BNS)-electroporation platform that could effectively capture CTCs and allow for downstream regulation and monitoring of their intracellular activities in a real-time and manner. The BNSs possessed numerous nanobranches on the outer sidewall of hollow nanotubes, which could be conjugated with specific antibodies to facilitate the effective capture of CTCs. Nanoelectroporation could be applied through the BNSs to nondestructively porate the membranes of the captured cells at a low voltage, allowing the delivery of exogenous biomolecules into the cytosol and the extraction of cytosolic contents through the BNSs without affecting cell viability. The efficient delivery of biomolecules (e.g., small molecule dyes and DNA plasmids) into cancer cells with spatial and temporal control and, conversely, the repeated extraction of intracellular enzymes (e.g., caspase-3) for real-time monitoring were both demonstrated. This technology can provide new opportunities for the comprehensive understanding of cancer cell functions that will facilitate cancer diagnosis and treatment.
循环肿瘤细胞（CTC）的下游分析为癌症研究提供了新的见解。特别是，CTC 的检测，以及随后对其细胞内活动的调控和监测，可以为全面了解癌症发病机制和进展提供有价值的信息。然而，目前的 CTC 检测技术很少能够长时间地调控和监测癌细胞的细胞内微环境。在这里，我们开发了一种多功能分支纳米棒（BNS）-电穿孔平台，能够有效地捕获 CTC，并实时、有效地调控和监测其细胞内活动。BNSs 在中空纳米管的外侧壁上具有许多纳米分支，可以与特定的抗体结合，以促进 CTC 的有效捕获。纳米电穿孔可以通过 BNSs 应用于以低电压无损地穿孔捕获细胞的膜，允许外源性生物分子递送到细胞质中，并通过 BNSs 提取细胞质内容物，而不影响细胞活力。该技术可以高效地将生物分子（如小分子染料和 DNA 质粒）递送到具有时空控制的癌细胞中，并且可以反复提取细胞内酶（如 caspase-3）进行实时监测。这项技术为全面了解癌症细胞功能提供了新的机会，将有助于癌症的诊断和治疗。
