Abstract The culture and expansion of circulating tumor cells (CTCs) for ex vivo assays plays an important role in precision medicine. However, it still represents a big challenge in translational research. Generating knowledge about the characteristics of CTCs can help to shed light about the metastasis process. Furthermore, ex vivo culture of CTCs might allow performing functional analyses and testing different drugs, to guide clinical therapies. In this work, we present a new methodology based on the use of nanosystems to support ex vivo culture of CTCs. We have formulated oil-in-water (O/W) nanoemulsions (NEs) composed by lipids and fatty acids, and have demonstrated that they can help increasing cell viability on different breast cancer cell lines. Moreover, we have generated a CTC model from breast cancer mice xenografts, to prove the ability of the NEs to facilitate their culture and expansion. Additionally, we have postulated a mechanism of action based on the cell consumption of the NEs, which are acting as energy suppliers, driving proliferation. This work corroborates the potential of nanotechnology to provide valuable tools for precision oncology, and the ability of our NEs to improve proliferation of breast cancer CTCs for the establishment of CTCs culture protocols.

中文翻译：

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支持乳腺癌循环肿瘤细胞离体细胞培养的纳米乳剂

摘要 用于体外检测的循环肿瘤细胞 (CTC) 的培养和扩增在精准医学中发挥着重要作用。然而，它仍然是转化研究的一大挑战。生成关于 CTC 特征的知识有助于阐明转移过程。此外，CTC 的离体培养可能允许进行功能分析和测试不同的药物，以指导临床治疗。在这项工作中，我们提出了一种基于使用纳米系统支持 CTC 离体培养的新方法。我们配制了由脂质和脂肪酸组成的水包油 (O/W) 纳米乳液 (NE)，并证明它们可以帮助提高不同乳腺癌细胞系的细胞活力。此外，我们已经从乳腺癌小鼠异种移植物中生成了 CTC 模型，证明NEs促进其文化和扩张的能力。此外，我们假设了一种基于 NE 的细胞消耗的作用机制，这些 NE 充当能量供应商，推动增殖。这项工作证实了纳米技术为精准肿瘤学提供有价值工具的潜力，以及我们的 NE 提高乳腺癌 CTC 增殖以建立 CTC 培养协议的能力。