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Virus-based nanoparticles for detecting breast cancer biomarkers

基于病毒的纳米粒子用于检测乳腺癌生物标志物

基本信息

批准号：
9265843
负责人：
Chuanbin Mao
金额：
$ 33.83万
依托单位：
UNIVERSITY OF OKLAHOMA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2020-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9265843
关键词：
Bacteria Bacteriophage T7 Bacteriophages Binding Biological Markers Blood Cells Body Fluids Breast Cancer Cell Breast Cancer Detection Breast Cancer Patient Breast Cancer therapy Cancer Biology Cancer Etiology Cancer Patient Capsid Cells Color Competitive Binding Complex Data Detection Diagnosis Early Diagnosis Engineering Eye Family Fiber Fluorescence Gene Expression Genetic Engineering Genetic Transcription Goals Gold Human Human body Hybrids In Vitro Infection Lead Lytic Virus Magnetism Mammary Gland Parenchyma Mammary Neoplasms Mammography Methods MicroRNAs Nucleic Acids Nucleotides Oligonucleotides Peptides Phage Display Phosphate Buffer Plasma Polymerase Chain Reaction Property Proteins RNA Recombinants Reporting Reproducibility Reverse Transcription Risk Saline Sampling Series Serum Structure Tail Techniques Testing Time Tissues Tumor Tissue Untranslated RNA Virus Water Whole Blood Woman aqueous base breast cancer diagnosis cancer biomarkers cancer cell cancer therapy cancer type design human tissue improved malignant breast neoplasm millimeter mortality multiplex detection nanoparticle novel public health relevance targeted biomarker

项目摘要

Breast cancer is the most common type of cancer in women. Its traditional diagnosis methods either have low sensitivity or high rate of false positive, making early diagnosis of breast cancer challenging. This project aims to detect breast cancer-specific, non-invasive, non-coding nucleic acid biomarkers from the plasma, cancer cells and tumor tissues of human breast cancer patients, for the purpose of discovering a new method of early breast cancer diagnosis. Our method first uses phage-based nanoparticles to capture the breast cancer-specific nucleic acid biomarkers (the target molecules) to form a complex, which carries the concentration information of both target biomarkers and phages. Then the phages are separated from the complex and titered to determine the concentration of phages, which in turn leads to the quantification of the target biomarkers. Specifically, we will first find out the best conditions for the multiplexed detection of breast cancer-specific nucleic acid biomarkers in commercial human plasma in order to understand the effect of the parameters of the detection media on the detection sensitivity. We will then apply the same method to detect multiple breast cancer-specific target biomarkers from human breast cancer cells and tissues. Towards this end, the target biomarkers will be isolated from breast cancer cells and in vitro breast tumor tissues to form the solutions of the target biomarkers by using a commercial kit. Then we will detect and quantify the target biomarkers from the resultant solutions. We will also detect the target nucleic acid biomarkers from total RNA solutions isolated from tumor tissues of breast cancer patients. This project will lead to phage-based method that can detect breast cancer-associated nucleic acid biomarkers from the plasma, cancer cells and tumor tissues of human breast cancer patients with high sensitivity, accuracy and reproducibility.

乳腺癌是女性中最常见的癌症类型。传统的诊断方法要么敏感性低，要么假阳性率高，给乳腺癌的早期诊断带来了挑战。本项目旨在从人类乳腺癌患者的血浆、癌细胞和肿瘤组织中检测乳腺癌特异性、非侵入性、非编码的核酸生物标志物，以期发现乳腺癌早期诊断的新方法。我们的方法首先使用基于噬菌体的纳米颗粒捕获乳腺癌特异性核酸生物标志物（靶分子）形成复合物，该复合物同时携带靶生物标志物和噬菌体的浓度信息。然后将噬菌体从复合物中分离出来并滴度以确定噬菌体的浓度，这反过来导致目标生物标志物的定量。具体而言，我们将首先找出商业人血浆中乳腺癌特异性核酸生物标志物多路检测的最佳条件，以了解检测介质参数对检测灵敏度的影响。然后，我们将应用相同的方法从人类乳腺癌细胞和组织中检测多种乳腺癌特异性靶标生物标志物。为此，目标生物标志物将从乳腺癌细胞和体外乳腺肿瘤组织中分离出来，使用商业试剂盒形成目标生物标志物的溶液。然后，我们将从所得溶液中检测和量化目标生物标志物。我们还将从乳腺癌患者肿瘤组织中分离的总RNA溶液中检测目标核酸生物标志物。本项目将建立基于噬菌体的方法，从人类乳腺癌患者的血浆、癌细胞和肿瘤组织中检测乳腺癌相关核酸生物标志物，具有较高的灵敏度、准确性和重复性。