Novel Nano-Plasmonic Technology for Quantitative Analysis of Cancer Exosomes

用于癌症外泌体定量分析的新型纳米等离子体技术

• 批准号: 9526126
• 负责人: Hyungsoon Im
• 金额: $ 24.9万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9526126
• 关键词: Achievement; Address; Advisory Committees; Affinity; Aftercare; Ascites; Biological Markers; Biology; Blood; Brain Neoplasms; Cell Line; Cells; Clinical; DNA; Detection; Development; Disease; Doctor of Philosophy; Engineering; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; General Hospitals; Genetic Markers; Genetically Engineered Mouse; Glioblastoma; Goals; Human; Image; Imaging Techniques; International; Investigation; Label; Ligands; Light; MGMT gene; Malignant Neoplasms; Malignant neoplasm of ovary; Massachusetts; Measurement; Measures; Medical; Membrane; Mentors; Mentorship; Messenger RNA; Molecular; Molecular Probes; Molecular Profiling; Monitor; Names; Nanotechnology; Neoplasm Metastasis; Nucleic Acids; Oncologist; Performance; Phase; Phenotype; Phospholipids; Primary Neoplasm; Prognostic Marker; Proteins; RNA; Recurrence; Research; Research Personnel; Ribosomal Protein S6; Sampling; Scheme; Serum; Signal Transduction; Surface; System; Systems Biology; Techniques; Technology; Testing; Time; Training; Translational Research; Treatment Efficacy; Tumor-Derived; Vesicle; Work; analytical method; anticancer research; cancer biomarkers; cancer cell; cancer diagnosis; cancer invasiveness; cancer therapy; career; circulating biomarkers; clinical application; clinical practice; density; epidermal growth factor receptor VIII; exosome; experience; imaging modality; improved; interest; liquid biopsy; medical schools; member; microvesicles; mouse model; nanofabrication; nanoplasmonic; nanovesicle; next generation; novel; plasmonics; prototype; public health relevance; rapid technique; response; scale up; skills; stem; tool; treatment response; tumor; tumor progression

 DESCRIPTION (provided by applicant): The broad goal of this proposal is to develop and apply a novel sensing platform to detect and molecularly profile exosomes for monitoring tumor progression and treatment response in glioblastoma multiforme (GBM). Exosomes are membrane-bound phospholipid nanovesicles actively shed by cancer cells and the platform will be used to determine the abundance and composition of exosomes in serum. The candidate, Hyungsoon Im, has extensive experience in developing new sensing platforms with a background in engineering and now aims to transition to biomedical cancer research. Through the training, he will further develop skill sets to conduct independent translational research and make significant contribution to the field of cancer exosome research. This work will be conducted in the Center for Systems Biology at Massachusetts General Hospital and Harvard Medical School under the mentorship of Dr. Ralph Weissleder MD, PhD. To expand expertise, he has also brought in Xandra Breakefield, an internationally recognized expert in exosome biology and Prof. Antonio Chiocca, a neurosurgical oncologist with interest in translational work for additional mentoring and expertise. These members of the advisory committee will facilitate the transition of Hyungsoon's work toward a unique and independent line of investigation and allow him to develop a successful career as an independent biomedical cancer researcher. The research plan aims to first develop a microarray nano-plasmonic exosome sensing platform (nPLEX) for multiplexed profiling of exosome proteins and nucleic acids in serum. Exosomes have unique advantages as a circulating biomarker, but the quantification of their molecular composition has been challenging especially in clinical settings. This work stems from preliminary research using plasmonic nanoholes for sensitive detection of exosomes in a label-free manner and quantification of their marker expression levels. In specific aim 1, an advanced nPLEX platform with 400 sensing arrays will be developed by integrating with state-of-the- art nanofabrication techniques and a high-throughput readout system. In specific aim 2, the nPLEX platform will be applied for serial analyses of exosomes in GBM mouse models. Longitudinal assessment of exosomes pre- and post-treatment will be used to identify specific exosomes markers that correlate with tumor progression and treatment response to predict therapeutic efficacy. The proposed platform would allow comprehensive analyses of tumor-derived exosomes to shed light on molecular profiles of primary and metastatic tumors and provide information to guide efficient treatment schemes. The new nPLEX system could be a transformative tool facilitating cancer research and clinical practice.

 描述（由申请人提供）：该提案的总体目标是开发和应用一种新型传感平台来检测和分子分析外来体，以监测多形性胶质母细胞瘤（GBM）的肿瘤进展和治疗反应。外泌体是由癌细胞主动脱落的膜结合磷脂纳米囊泡，该平台将用于确定血清中外泌体的丰度和组成。候选人Hyungsoon Im在开发具有工程背景的新传感平台方面拥有丰富的经验，现在的目标是过渡到生物医学癌症研究。通过培训，他将进一步发展进行独立转化研究的技能，并为癌症外泌体研究领域做出重大贡献。这项工作将在马萨诸塞州总医院和哈佛医学院的系统生物学中心进行，由Ralph Weissleder博士指导。为了扩大专业知识，他还带来了Xandra Breakefield，一位国际公认的外泌体生物学专家和Antonio Chiocca教授，一位对翻译工作感兴趣的神经外科肿瘤学家，以获得更多的指导和专业知识。咨询委员会的这些成员将促进Hyungsoon的工作向独特和独立的调查方向过渡，并使他能够作为一名独立的生物医学癌症研究人员发展成功的职业生涯。该研究计划旨在首先开发一种微阵列纳米等离子体外泌体传感平台（nPLEX），用于血清中外泌体蛋白和核酸的多重分析。外泌体作为循环生物标志物具有独特的优势，但其分子组成的定量一直具有挑战性，特别是在临床环境中。这项工作源于使用等离子体纳米孔以无标记方式灵敏检测外泌体及其标记物表达水平的初步研究。在具体目标1中，将通过与最先进的纳米纤维技术和高通量读出系统相结合，开发具有400个传感阵列的先进nPLEX平台。在具体目标2中，nPLEX平台将用于GBM小鼠模型中外来体的系列分析。治疗前和治疗后外泌体的纵向评估将用于鉴定与肿瘤进展和治疗反应相关的特异性外泌体标志物，以预测治疗功效。拟议的平台将允许对肿瘤来源的外泌体进行全面分析，以揭示原发性和转移性肿瘤的分子特征，并提供信息以指导有效的治疗方案。新的nPLEX系统可能成为促进癌症研究和临床实践的变革性工具。