新型诊断和治疗性AuNP-Cy5-ASODN分子探针体系的建立及其对恶性肿瘤分子成像与治疗评价的研究

项目名称： 新型诊断和治疗性AuNP-Cy5-ASODN分子探针体系的建立及其对恶性肿瘤分子成像与治疗评价的研究

项目编号： No.30872410

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 王梅

作者单位： 西安交通大学

项目金额： 31万元

中文摘要： 通过干扰肿瘤细胞异常表达基因的肿瘤分子治疗取得了突破性进展，但分子水平的无创活细胞实时定量早期诊断和治疗评价仍然是肿瘤分子治疗亟待解决的关键问题。基于前期研究取得的成果和积累的技术手段，以凋亡抑制基因Survivin为靶标，拟建立高灵敏、高特异性分子识别体系，动态检测肿瘤细胞中靶基因转录水平表达，在细胞学变化前从临床样本中发现肿瘤细胞，评价肿瘤对靶向治疗药物反应性。将前期已成功筛选并证明其作用的Survivin反义寡核苷酸作为检测基因mRNA表达的识别序列，利用纳米金的基因载体和荧光淬灭特性，建立Survivin反义寡核苷酸纳米金和荧光Cy5互补探针，调控Survivin基因表达和无创实时可视基因表达水平。通过可视分子特异性信号，对恶性肿瘤早发现、早治疗，能对多数恶性肿瘤的分子干扰治疗进行评价，提高治疗的针对性和有效性，降低恶性肿瘤死亡率，为恶性肿瘤的诊治提供新的有价值的工具。

中文关键词： 恶性肿瘤；纳米金-Cy5双标探针；Survivin反义寡核苷酸；早期诊断；治疗评价

英文摘要： One of the most difficult challenges of oncology is to development of novel approaches for quantitative analysis of gene expression in intact tumor cells， which is crucial for cancer detection and for studying the response of cancer cells to biological and therapeutic reagents. Survivin is a member of the inhibitor of apoptosis protein family that plays a crucial role in the apoptosis resistance of tumor cells and is overexpressed on almost all human cancer types and cell lines, we designed a novel survivin antisense oligonucleotide-modified gold nanoparticle probe hybridized to fluorophore （Cy5） complements can be used as both intracellular gene regulation agents and cellular signal for noninvasive visualizing and quantifying RNA in living cells. The novel probe take advantage of the highly efficient fluorescence quenching properties of gold and cellular uptake of oligonucleotide nanoparticle conjugates, thus overcoming many of the challenges to creating sensitive and effective intracellular probes. Using antisense oligonucleotide-modified gold nanoparticle probes in the imaging and silencing of survivin could potentially be useful in detecting and treating precancerous lesions. The modified probe may provide promising new ways to evaluate mRNA expression and serve as useful tools for dual imaging and therapy in clinical oncology research. Finally, the probe has a potential to greatly aid in screening prospective patients for early cancer detection and in monitoring the efficacy of drug therapy.

英文关键词： survivin antisense oligonucleotide;gold nanoparticle;cancer;early cancer detection;the efficacy of drug therapy