School of Chemistry, University of Edinburgh, Edinburgh, UK.
School of Medicine, University of St Andrews, St Andrews, UK.
J Biophotonics. 2019 May;12(5):e201800201. doi: 10.1002/jbio.201800201. Epub 2019 Jan 9.
There has been increasing use of in vitro cell culture models that more realistically replicate the three-dimensional (3D) environment found in vivo. Multicellular tumor spheroids (MTS) using cell lines or patient-derived organoids have become an important in vitro drug development tool, where cells are grown in a 3D "sphere" that exhibits many of the characteristics found in vivo. Significantly, MTS develop gradients in nutrients and oxygen, commonly found in tumors that contribute to therapy resistance. While MTS show promise as a more realistic in vitro culture model, there is a massive need to improve imaging technologies for assessing biochemical characteristics and drug response in such models to maximize their translation into useful applications such as high throughput screening (HTS). In this study, we investigate the potential for Raman spectroscopy to unveil biochemical information in MTS and have investigated how spheroid age influences drug response, shedding light on increased therapy resistance in developing tumors. The wealth of molecular level information delivered by Raman spectroscopy in a noninvasive manner, could aid translation of these 3D models into HTS applications.
越来越多的人开始使用体外细胞培养模型，这些模型更真实地模拟了体内的三维（3D）环境。使用细胞系或患者来源的类器官的多细胞肿瘤球体（MTS）已成为一种重要的体外药物开发工具，其中细胞在 3D“球体”中生长，该球体表现出许多体内存在的特征。重要的是，MTS 中会出现营养物质和氧气的梯度，这在导致治疗耐药性的肿瘤中很常见。虽然 MTS 作为更真实的体外培养模型显示出一定的前景，但仍迫切需要改进成像技术，以评估此类模型中的生化特征和药物反应，从而最大程度地将其转化为高通量筛选（HTS）等有用的应用。在这项研究中，我们研究了拉曼光谱在揭示 MTS 中的生化信息方面的潜力，并研究了球体年龄如何影响药物反应，从而揭示了正在发育的肿瘤中治疗耐药性的增加。拉曼光谱以非侵入性的方式提供了丰富的分子水平信息，这可能有助于将这些 3D 模型转化为 HTS 应用。
