Spatially resolved quantification of drug metabolism and efficacy in 3D paper-based tumor mimics.
Spatially resolved quantification of drug metabolism and efficacy in 3D paper-based tumor mimics.
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DOI：
10.1016/j.aca.2021.339091
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发表时间：
2021-11-22
影响因子：
6.2
通讯作者：
Lockett MR
中科院分区：
文献类型：
--
作者：
Larson TS;Glish GL;Lockett MR
纸基培养物是用于制备三维 (3D)、组织和肿瘤样结构的新兴平台。堆叠单张含细胞纸的能力提供了组装具有确定的细胞组成和微环境的结构的模块化方法。这些分层堆叠在实验结束时很容易分离，提供空间分辨的活细胞群以供进一步分析。在这里，我们描述了一个工作流程，其中可以以空间解析的方式量化细胞活力、药物渗透和药物代谢。具体来说，我们利用液相色谱-质谱法 (LC-MS) 绘制了药物伊立替康及其生物活性代谢物 SN38 在含有结直肠癌细胞的堆叠结构中的分布。本文提供了第一个 3D 培养平台的示例，该平台以空间解析的方式量化活力和药物代谢。我们的数据表明，这种堆叠结构模仿了实体瘤中的观察结果。堆叠底部的细胞比与培养基接触的层更具有耐药性，类似于增殖肿瘤营养贫乏中心的细胞比肿瘤外围快速分裂的细胞更具有耐药性。定量活力和药物代谢测量的强大结合将使未来的研究能够确定肿瘤不同区域耐药性的确切机制。
Paper-based cultures are an emerging platform for preparing three-dimensional (3D), tissue- and tumor-like structures. The ability to stack individual sheets of cell-containing paper affords a modular means of assembling structures with defined cellular compositions and microenvironments. These layered stacks are easily separated at the end of an experiment, providing spatially resolved populations of live cells for further analysis. Here we describe a workflow in which cell viability, drug penetration, and drug metabolism can be quantified in a spatially resolved manner. Specifically, we mapped the distribution of the drug irinotecan and its bioactive metabolite SN38 in a colorectal cancer cells-containing stacked structure with liquid chromatography-mass spectrometry (LC-MS). This paper provides the first example of a 3D culture platform that quantifies viability and drug metabolism in a spatially resolved manner. Our data show that this stacked structure mimics observations in solid tumors. Cells at the bottom of the stack are more drug-resistant than layers in contact with the culture medium, similar to cells in the nutrient-poor center of a proliferating tumor being more drug-resistant than rapidly dividing cells at a tumor's periphery. The powerful combination of quantitative viability and drug metabolism measurements will enable future studies to determine the exact mechanism(s) of drug resistance in different regions of a tumor.
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影响因子：
24.3
作者：
Correia, Ana Luisa;Bissell, Mina J.
通讯作者：
Bissell, Mina J.
影响因子：
4.3
作者：
Lukowski, Jessica K.;Hummon, Amanda B.
通讯作者：
Hummon, Amanda B.
DOI：
10.1007/s13361-014-1071-0
发表时间：
2015-04-01
影响因子：
3.2
作者：
Liu, Xin;Hummon, Amanda B.
通讯作者：
Hummon, Amanda B.
影响因子：
4.5
作者：
de Man FM;Goey AKL;van Schaik RHN;Mathijssen RHJ;Bins S
通讯作者：
Bins S
影响因子：
17.1
作者：
Basuki, Johan S.;Duong, Hien T. T.;Davis, Thomas P.
通讯作者：
Davis, Thomas P.