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: 9146855
• 负责人: Hyungsoon Im
• 金额: $ 16.46万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-21 至 2017-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9146855
• 关键词: Achievement; Address; Advisory Committees; Affinity; Aftercare; Ascites; Binding; Biological Markers; Biology; Blood; Brain Neoplasms; Cell Line; Cells; Clinical; DNA; Detection; Development; Diagnostic Neoplasm Staging; 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; Health; Human; Image; Imaging Techniques; Investigation; Label; Ligands; Light; MGMT gene; Malignant Neoplasms; Malignant neoplasm of ovary; Massachusetts; Measurement; Measures; Medical; Membrane; Mentors; Mentorship; Messenger RNA; Methods; 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 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; 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）：该提案的主要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泌体，以监测多形性胶质母细胞瘤（GBM）的肿瘤进展和治疗反应。外泌体是主动膜结合的磷脂纳米囊泡。候选人 Hyungsoon Im 在开发新的传感平台方面拥有丰富的经验。他拥有工程学背景，现在的目标是转向生物医学癌症研究。通过培训，他将发展进一步的技能来进行独立的转化研究，并为癌症外泌体研究领域做出重大贡献。这项工作将在系统中心进行。在马萨诸塞州总医院和哈佛医学院的生物学领域，在 Ralph Weissleder 医学博士、博士的指导下，为了扩展专业知识，他还聘请了国际公认的外泌体生物学专家 Xandra Breakefield 和神经外科肿瘤学家 Antonio Chiocca 教授。咨询委员会的这些成员将促进 Hyungsoon 的工作向独特且独立的研究方向转变，并使他能够作为一名独立的生物医学癌症研究员发展成功的职业生涯。首先开发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，但其分子组成的量化还存在一定的困难。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并量化其标记物表达水平的初步研究。在具体目标 1 中，将通过与 State-of 集成来开发具有 400 个传感阵列的先进 nPLEX 平台。 -最先进的纳米加工技术和高通量读出系统在具体目标 2 中，nPLEX 平台将应用于 GBM 小鼠外泌体的连续分析。治疗前和治疗后外泌体的纵向评估将用于识别与肿瘤进展和治疗反应相关的特定外泌体标记物，以预测治疗效果。新的 nPLEX 系统可以成为促进癌症研究和临床实践的变革性工具。