纳米电化学生物传感器快速检测消化道肿瘤多药耐药基因的新方法研究

Gastrointestinal cancer endangers human health seriously, and the tolerability of cancer has become the primary reason which causes the failure in the gastrointestinal cancer therapy. The specific biological marker of cancer cell multidrug resistance is multidrug resistance gene MDR1. The sensitivity and tolerability of chemotherapeutics in patients can be predicted by the detection of MDR1 gene expression. Then the reasonable chemotherapy regimen and sensitive chemotherapy drugs can be chosen scientifically to improve curative effect and survival rate signally. Now, the major clinical testing methods include fluorescence in situ hybridization, flow cytometry, RT-PCR, and so on. But there are some limitations in these methods, such as poor specificity and sensitivity, fussy operation and high costs, which restrict clinical application. Novel nanoelectrochemical biosensor, which combines nanotechnology, biosensing technology and molecular hybridization technique, is first developed for sensitive rapid, simple and economical detection of multidrug resistance gene by our research group through design of high-specificity nanobiological probe connected with nanoparticle labeling technique. It would provide research foundation for clinical application and detection of other multidrug resistance genes in cancer. And it also would provide the scientific proof for the doctors to formulate reasonable chemotherapy regimen for personalized medicine. Thus, this interdisciplinary study shows prominent academic innovation and clinical application value.

消化道恶性肿瘤严重危害着人类健康，而肿瘤耐受性是消化道肿瘤治疗失败的主要原因。肿瘤细胞多药耐药的特异性生物标志物是多药耐药基因MDR1。通过检测 MDR1基因表达，可预测患者对化疗药物的敏感性和耐受性，科学选择合理的化疗方案和敏感的化疗药物，显著提高疗效和生存率。目前检测消化道恶性肿瘤耐药MDR1基因的方法包括荧光原位杂交、流式细胞术、RT-PCR技术等，它们分别存在特异性、敏感度不高、操作繁琐、检测费用高等问题，限制了在临床中的应用。本项目首次提出将纳米技术、酶联免疫分析技术与锁核酸探针技术有机结合，构建新型纳米电化学生物传感器，通过制备高特异性锁核酸生物分子探针，结合纳米粒子标记技术，建立灵敏、快速、简便经济的MDR1基因检测新方法，为尽快应用于临床肿瘤耐药基因检测提供研究基础，并为临床医生制定合理的个体化肿瘤化疗方案提供科学依据。因而本跨学科研究具有较突出的学术创新性和临床应用价值。

消化道恶性肿瘤严重危害着人类健康，而肿瘤耐受性是消化道肿瘤治疗失败的主要原因。肿瘤细胞多药耐药的特异性生物标志物是多药耐药基因MDR1。通过检测MDR1基因表达，可预测患者对化疗药物的敏感性和耐受性，科学选择合理的化疗方案和敏感的化疗药物，显著提高疗效和生存率。目前检测消化道恶性肿瘤耐药MDR1基因的方法包括荧光原位杂交、流式细胞术、RT-PCR技术等，它们分别存在特异性、敏感度不高、操作繁琐、检测费用高等问题，限制了在临床中的应用。本项目通过对消化道恶性肿瘤多药耐药MDR1基因探针的设计，制备了多孔纳米金、石墨烯/碳纳米管/纳米金复合材料等新型纳米材料，进行了分子探针在修饰纳米材料的传感器表面固定化研究，构建了多种新型纳米电化学生物传感器，在实验条件优化下，建立了用于消化道恶性肿瘤多药耐药MDR1基因检测的新方法。该方法灵敏准确、简便经济、重现性和稳定性好，将为应用于临床肿瘤耐药基因的检测提供科学研究基础，并为临床制定合理的个体化肿瘤化疗方案提供科学依据。