College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023, China.
Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
Angew Chem Int Ed Engl. 2023 Aug 1;62(31):e202302000. doi: 10.1002/anie.202302000. Epub 2023 May 23.
Colonization of cancer cells at secondary sites, a decisive step in tumor metastasis, is strongly dependent on the formation of metastatic microenvironments regulated by intrinsic single-cell metabolism traits. Herein, we report a single-cell microfluidic platform for high-throughput dynamic monitoring of tumor cell metabolites to evaluate tumor malignancy. This microfluidic device empowers efficient isolation of single cells (>99 %) in a squashed state similar to tumor extravasation, and employs enzyme-packaged metal-organic frameworks to catalyze tumor cell metabolites for visualization. The microfluidic evaluation was confirmed by in vivo assays, suggesting that the platform allowed predicting the tumorigenicity of captured tumor cells and screening metabolic inhibitors as anti-metastatic drugs. Furthermore, the platform efficiently detected various aggressive cancer cells in unprocessed whole blood samples with high sensitivity, showing potential for clinical application.
癌细胞在次级部位的定植是肿瘤转移的决定性步骤，强烈依赖于由内在单细胞代谢特征调控的转移性微环境的形成。在此，我们报告了一种用于高通量动态监测肿瘤细胞代谢物以评估肿瘤恶性程度的单细胞微流控平台。该微流控装置能够高效分离类似肿瘤渗出的压扁状态下的单细胞（>99%），并采用酶封装的金属-有机框架来催化肿瘤细胞代谢物以进行可视化。微流控评估通过体内实验得到证实，表明该平台可以预测捕获的肿瘤细胞的致瘤性，并筛选代谢抑制剂作为抗转移药物。此外，该平台能够高效地从未经处理的全血样本中检测到各种侵袭性癌细胞，具有较高的灵敏度，显示出临床应用的潜力。
