基于微流控芯片活细胞水平抗肿瘤药效评价新方法研究

Based on Microfluidic chip as analysis platform, the project carried out a systematic and in-depth study for the key issues of antitumor pharmacodynamic evaluation at the cellular level. The study found that there were few types of biomarkers for anticancer activity evaluation and even most of biomarkers were biomacromolecules, whose detection and analysis need the application of complicated and expensive molecular biology, immunological technology. To address these problems, Our research focus is to find small molecules closely related to the anti-tumor efficacy as new biomarkers, and then to develop analytical methods for these small molecules with high sensitivity and selectivity, and ultimately to give multi-faceted antitumor pharmacodynamic evaluation using the variation of a variety of intracellular and extracellular small molecules as indicators for improving the efficacy of anticancer drugs. On this basis, we focus on establishing scientific, accurate, fast, efficient, low-cost antitumor pharmacodynamic evaluation platforms and drug activity screening platforms in the level of living cells for pharmacodynamic evaluation of monotherapy and the drug combination, and then clarifying pharmacological mechanism of antitumor drugs on the the molecular level.

本项目以微流控芯片为分析平台，针对基于微流控芯片活细胞水平抗肿瘤药效评价以及药物活性测试存在的关键问题开展了系统而深入的研究。研究发现用于抗肿瘤药效评价的生物标志物种类有限并且已有标志物大多为生物大分子，其检测和分析需要复杂昂贵的生物免疫技术，所以我们的研究目标是寻找与抗肿瘤药效相关的生理小分子为新标志物，发展高灵敏，高选择的小分子分析检测技术，以细胞内外多种小分子的变化规律为指标来多方位地进行抗肿瘤药效评价，以期提高抗肿瘤药物的疗效。在此基础上，基于微流控芯片建立一套在活细胞水平上科学，准确，快速，高效，低成本的抗肿瘤药效评价分析平台以及药物活性筛选平台用于多种抗肿瘤药物单独用药和联合用药的药效评价，进而对抗肿瘤药物作用于细胞的机制进行分子水平的深入研究。

本项目针对用于抗肿瘤药效评价的生物标志物种类有限并且已有标志物大多为生物大分子，其检测和分析需要复杂昂贵的生物免疫技术等问题，提出了以生理小分子为生物标志物进行抗肿瘤药效评价，并结合微流控芯片和微阵列电极，以此建立药效评价筛选分析平台。在建立药效评价筛选平台的同时，进而发展了多种生理小分子的电学，光学分析检测方法。（1）基于电化学阻抗法研究了氧化石墨烯，还原石墨烯，石墨烯与明胶，石墨烯与多聚赖氨酸复合物作为活细胞生长基底的药物敏感性研究；（2）首次设计即插即用装置完成对吡唑并菲类化合物体外抗肿瘤活性的快速筛选；（3）基于电化学方法研究抗肿瘤药物阿霉素诱导肿瘤细胞凋亡过程中细胞膜通透性变化引起的还原型谷胱甘肽的含量变化；（4）基于糖基电化学传感阵列发展的高灵敏检测癌胚抗原的电化学传感器。发表论文22篇，其中SCI源刊论文4篇，CSCD核心源7篇，核心11篇；带教本科毕业生6名。