Vickers Dwayne A L, Ouyang Mengxing, Choi Chris Hyunseok, Hur Soojung Claire
The Rowland Institute at Harvard University , 100 Edwin H. Land Boulevard, Cambridge, Massachusetts 02142, United States.
Anal Chem. 2014 Oct 21;86(20):10099-105. doi: 10.1021/ac501479g. Epub 2014 Oct 7.
Combination therapy has become one of the leading approaches for treating complex diseases because it coadministers clinically proven drugs to concurrently target multiple signaling pathways of diseased cells. Identification of synergic drug combinations at their respective effective doses without unwanted accumulative side effects is the key to success for such therapy. In this work, we demonstrate the feasibility of the vortex-assisted microfluidic electroporation system for direct drug cocktail analyses where drug substances were individually delivered into cytosols in a sequential and dosage-controlled manner. Through quantitative analyses, the synergic combinational dosage ratios of the chemotherapeutic drug and the anticancer flavonoid were identified. When integrated with high-throughput label-free rare cell purification techniques, the presented system has the potential for development of personalized medicines as the system would be capable of comprehensively assessing drug combinations directly on patients' cellular samples.
联合疗法已成为治疗复杂疾病的主要方法之一，因为它同时施用经临床验证的药物，以同时靶向患病细胞的多个信号通路。在各自有效剂量下鉴定具有协同作用的药物组合且无不良累积副作用，是这种疗法成功的关键。在这项工作中，我们展示了涡旋辅助微流控电穿孔系统用于直接药物鸡尾酒分析的可行性，其中药物物质以顺序和剂量控制的方式分别递送至细胞质中。通过定量分析，确定了化疗药物和抗癌类黄酮的协同组合剂量比。当与高通量无标记稀有细胞纯化技术相结合时，所提出的系统具有开发个性化药物的潜力，因为该系统能够直接在患者的细胞样本上全面评估药物组合。
