Multiplexed analysis of exosomes in cancer nano therapy

癌症纳米疗法中外泌体的多重分析

基本信息

批准号：
9487955
负责人：
RALPH WEISSLEDER, MD, PHD
金额：
$ 38.9万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
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：
2016-06-15 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9487955
关键词：
Affinity Biological Assay Biological Testing Blood Circulation Blood Platelets Cancer Patient Cells Clinic Clinical Core Biopsy Detection Diagnostic Procedure Drug resistance Elements Endothelial Cells Erythrocytes Evaluation Event Film Generations Goals Gold Image Immunocompetent Leukocytes Ligands Malignant Neoplasms Malignant neoplasm of ovary Measures Mesothelial Cell Messenger RNA Methods Microfluidics Modeling Molecular Molecular Analysis Molecular Profiling Monitor Mus Nanotechnology Noise Outcome Parents Patients Periodicity Pharmaceutical Preparations Printing Process Protein Analysis Proteins RNA Retrieval Sampling Series Serum Signal Transduction Specimen Surface System Systems Biology Techniques Technology Therapeutic Therapeutic Trials Time Tumor-Derived Vesicle anticancer research base cancer cell cancer therapy chemotherapy clinical practice cost cost effective design drug efficacy exosome experimental study human model improved innovation insight lithography macrophage method development mouse model nano nanoencapsulated nanoparticle nanoplasmonic nanotherapeutic nanotherapy new technology peripheral blood point of care point-of-care diagnostics protein biomarkers protein expression protein profiling public health relevance rapid technique response scale up sensor therapeutic nanoparticles transmission process tumor tumor initiation tumor progression validation studies

项目摘要

DESCRIPTION (provided by applicant): Detection of reliable markers of therapy response and drug resistance remains a major clinical challenge in ovarian cancer. This is particularly true for a series of nanotherapeutics entering the clinical arena. One little explored opportunity lies in the analysis of exosomes, 50-200 nm sized vesicles continuously shed into the circulation. Importantly such tumor derived exosomes are abundant (1011 vesicles/ml of peripheral blood in cancer patients), are fairly stable over time and contain proteins reflective of those found in parent tumors. A current major challenge and opportunity is the development of methods for rapidly determining the abundance and composition of cMVs from clinical samples. We have recently developed a highly sensitive, nanotechnology-based, point-of-care diagnostic method termed nPLEX (nano Plasmonic Exosome) which comprises periodic nanohole arrays fabricated in an opaque gold film for transmission plasmon imaging (Nat Biotechnol 2014;32, 490-5). We have shown that i) such analyses are exquisitely sensitive, ii) allow profiling of dozens of proteins on and inside exosomes thus allowing cell of origin studies and iii) that nPLEX analysis allows sophisticated therapy assessment. The goal of this application is to advance the nPLEX technology by i) expanding it to allow parallel profiling of protein and RNA, ii) validating it as a therapeutic read-out of nanoparticle therapeutics in mouse models and in the clinic. We hypothesize that the approach will be more sensitive and comprehensive in exosomal analysis than is currently possible and allow treatment evaluation. The proposed integrated profiling method has the potential to transform nano therapeutic trials, cancer research and clinical practice. It will enable objective therapeutic read-outs, events that occur before conventional clinical metrics. It will facilitate extensive profiling of exosome in paucicellular clinical specimens, significantly reduce costs, and can be easily combined with other downstream analyses.

描述（由适用提供）：检测可靠的治疗反应和耐药性标志物仍然是卵巢癌的主要临床挑战。尤其如此一系列进入临床领域的纳米疗法。一个小小的探索机会在于外泌体分析，50-200 nm大小的蔬菜不断散发到循环中。重要的是，这种衍生的外泌体含量丰富（癌症患者的1011蔬菜/毫升外周血），随着时间的流逝稳定，含有反映在父肿瘤中的蛋白质。当前的主要挑战和机会是开发快速确定临床样本中CMV的抽象和组成的方法。我们最近开发了一种高度敏感的，基于纳米技术的基于NPLEX（纳米等离子体外显体），该方法包括在不透明的金膜中制造的定期纳米钻阵列，用于传输等离子成像（Nat Biotechnol 2014; 32，490-5）。我们已经表明，i）此类分析完全敏感，ii）允许在外部外和内部进行数十种蛋白质进行分析，从而允许原产研究细胞和III）NPLEX分析允许复杂的治疗评估。该应用的目的是通过i）扩展它来推进NPLEX技术，以允许蛋白质和RNA并行分析，ii）将其验证为小鼠模型中纳米粒子疗法的治疗读数，并在小鼠模型中和在诊所。我们假设该方法在外部分析中比目前可能更敏感和全面，并允许治疗评估。拟议的综合分析方法具有改变纳米治疗试验，癌症研究和临床实践的潜力。它将实现客观的治疗读数，这是在常规临床指标之前发生的事件。它将促进在Paucityllular临床标本中的外泌体广泛分析，可显着降低成本，并可以轻松与其他下游分析结合使用。