In this paper, we present a 3D printed tumor spheroidal model suitable for drug discovery. This model is based on a hydroxyethyl cellulose/alginate/gelatin (HCSG) composite biomaterial that has three distinct properties: (1) the HCSG is similar to the commercial basement membrane extract in Ki67, MUC1, and PARP1 expressions of MCF-7 cells for embedding culture; (2) the HCSG is printable at room temperature; and (3) the HCSG can be large-scale manufactured at an ultralow cost. We printed a 3D MCF-7 spheroid model with HCSG and characterized it in terms of cell viability, spheroid size, key protein expression, and mitochondrial metabolic activity. We used the 3D MCF-7 spheroid model to evaluate the anti-breast cancer activity of 13 amino acid-based flavone phosphoramidates and found that the alanine structure induced a stronger drug resistance, whereas phenylalanine hardly caused drug resistance in the MCF-7 cells. This is the first time that 3D bioprinting technology has been used in a structure–activity relationship study.

中文翻译：

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用于结构-活性关系研究的3D生物打印乳腺肿瘤模型

在本文中，我们提出了适合药物发现的3D打印肿瘤球模型。该模型基于具有三个不同特性的羟乙基纤维素/藻酸盐/明胶（HCSG）复合生物材料：（1）HCSG与商业基底膜提取物类似，用于MCF-7细胞的Ki67，MUC1和PARP1表达嵌入文化；（2）HCSG可在室温下打印；（3）HCSG可以超低成本大规模生产。我们用HCSG打印了3D MCF-7球体模型，并根据细胞活力，球体大小，关键蛋白表达和线粒体代谢活性对其进行了表征。我们使用3D MCF-7球体模型评估了13种基于氨基酸的黄酮磷酸氨基甲酸酯的抗乳腺癌活性，发现丙氨酸结构诱导了更强的耐药性，而苯丙氨酸几乎不引起MCF-7细胞的耐药性。这是3D生物打印技术首次用于结构-活性关系研究中。