Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, P. R. China.
Lab Chip. 2023 May 30;23(11):2654-2663. doi: 10.1039/d3lc00251a.
Multicellular tumor spheroids (MCTSs) are solid tumor models with physiological relevance. To achieve robust process control, a MCTS fabrication method that combines cell membrane engineering and droplet microfluidic techniques is designed. The fluidic control and the chemical interactions between biotin and streptavidin enable artificial cell aggregation to be accomplished in seconds. Then, spheroids with a uniform size are fabricated within alginate microcapsules. Microfluidic mixing-based cell aggregation regulates the cell aggregate size and the spheroid composition, and the microcapsules regulate the size of spheroids from 120 to 180 μm. The method shows applicability for various cancer cell lines, including HCT116, HepG2, and A549. In addition, composite colon cancer spheroids consisting of HCT116 and NIH3T3 with predetermined cell ratios and uniform distributions are produced. The generated MCTSs are assessed using the ELISA and UPLC-MS/MS techniques. The release of vascular endothelial growth factor (VEGF) and the 5-fluorouracil (5-FU) resistance differ in the monotypic and cocultured colon cancer models. Our method provides a robust way to produce consistent and customized MCTSs in cancer research and drug screening.
多细胞肿瘤球体（MCTS）是具有生理相关性的实体瘤模型。为了实现稳健的过程控制，设计了一种将细胞膜工程和液滴微流控技术相结合的 MCTS 制造方法。流体控制和生物素与链霉亲和素之间的化学相互作用使得人工细胞聚集能够在几秒钟内完成。然后，在藻酸盐微胶囊内制造出具有均匀尺寸的球体。基于微流混合的细胞聚集调节细胞聚集体的大小和球体的组成，微胶囊调节球体的大小从 120 到 180μm。该方法适用于各种癌细胞系，包括 HCT116、HepG2 和 A549。此外，还产生了由 HCT116 和 NIH3T3 组成的具有预定细胞比和均匀分布的复合结肠癌球体。使用 ELISA 和 UPLC-MS/MS 技术评估生成的 MCTS。在单型和共培养结肠癌模型中，血管内皮生长因子（VEGF）的释放和 5-氟尿嘧啶（5-FU）的耐药性不同。我们的方法为癌症研究和药物筛选提供了一种生产一致和定制的 MCTS 的可靠方法。
