Application of QDs-based nanotyping technology in the evaluation of chemotherapy

描述（由申请人提供）：这个SBIR项目的目标是开发一种多路复用方法来同时量化异质肿瘤组织中生物标志物的表达水平。目前生物标志物的诊断和预后分类方法是基于免疫组织化学（IHC）。然而，基于免疫酶（HRP）的免疫组化方法具有单色性质，无法进行多路分子分析。此外，免疫组化仍然是半定量和主观的，导致观察者之间的结果有相当大的差异。量子点是一类新型的生物检测标签，在生物医学领域有着广泛的应用。它允许生物标志物检测和分析高度异质的样品和罕见的细胞群。多路QD技术可用于在单细胞水平上检查一组癌症生物标志物（原位分析），这是其他类型的基于纳米技术的分析所不可能做到的。NIH SBIR项目旨在开发一种基于qds的纳米分型方法来监测前列腺癌的化疗效果。具体来说，抗凋亡的缓激肽-survivin信号通路的激活是前列腺癌细胞对多西他赛（taxoere）耐药的关键，因此，缓激肽-survivin可以作为新的生物标志物来预测激素难治性前列腺癌患者的化疗反应。我们将建立一种基于多路qds的微创技术来监测慢激肽-生存素通路的激活状态，以评估前列腺癌模型的化疗效果。在SBIR一期项目中，我们将制备具有高生物亲和性和低非特异性结合的高质量量子点。此外，qd抗体偶联物将用于预测人类前列腺癌异种移植模型对多西他赛化疗的反应。在第二阶段，我们的重点将转移到提高拟议系统的灵敏度和发展量化方法。本项目最终交付的将是一款高灵敏度、临床适用的用于前列腺肿瘤成像的Ab-QD偶联试剂盒，用于预测化疗的反应。公共卫生相关性：前列腺癌（PCa）是美国男性中最常见的癌症。2007年，美国估计有218,890例新的前列腺癌病例被诊断出来。加强对癌症治疗的监测对提高患者的生存率至关重要。提出的量子点纳米分型技术将提供一个监测化疗疗效的平台，并指导医生做出适当的治疗决策。该项目的成功开发可以大大提高这些患者的生存率。

DESCRIPTION (provided by applicant): The goal of this SBIR project is to develop a multiplexing method to simultaneously quantify the expression levels of biomarkers in heterogeneous tumor tissue. The current method for diagnostic and prognostic classifications of biomarkers is based on immunohistochemistry (IHC). However, the immunoenzyme (HRP- based) IHC method has a single color nature and is unable to perform multiplexed molecular profiling. Moreover, IHC remains semi-quantitative and subjective, resulting in considerable inter-observer variation in results. Quantum dots (QD) are a new class of biological detection labels which present a broad range of biomedical applications. It allows biomarker detection and analysis in highly heterogeneous samples and rare cell populations. The multiplexed QD technology can be used to examine a panel of cancer biomarkers on the level of single cells (in situ analysis), which is not possible with other types of nanotechnology-based assays. This NIH SBIR project intends to develop a QDs-based nanotyping method to monitor the chemotherapy efficacy in prostate cancer. Specifically, activation of the anti-apoptotic bradykinin-survivin signaling pathway was found to be critical to Docetaxel (Taxotere) resistance in prostate cancer cells, therefore, bradykinin- survivin could be used as novel biomarkers to predict the chemotherapy response in hormone-refractory prostate cancer patients. We will establish a multiplexed QDs-based, minimally-invasive technology to monitor the activation status of the bradykinin-survivin pathway for evaluating chemotherapy efficacy in prostate cancer models. In this SBIR phase I project, we will prepare high quality QDs with high bio-affinities and low non- specific binding. Furthermore, the QD-antibody conjugates will be tested in the prediction of response to docetaxel chemotherapy in a human prostate cancer xenograft model. In Phase II, our focus will be shifted to improving the sensitivity of the proposed system and developing a quantification method. The final delivery of this project will be a highly sensitive, clinically applicable Ab-QD conjugation kit for prostate tumor imaging that will predict the response of chemotherapy. PUBLIC HEALTH RELEVANCE: Prostate cancer (PCa) is the most common cancer occurring among men in the United States. In 2007, an estimated 218,890 new cases of PCa were diagnosed in the U.S. Enhancing monitoring cancer therapy is very critical to increase the survival rate of patients. The proposed QD nanotyping technology will provide a platform to monitor chemotherapy efficacy and guide physicians in making decisions for the appropriate therapy. The successful development of this project can greatly increase the survival rate of these patients.