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（由适用提供）：该提案的广泛目标是开发和应用一个新型的传感平台来检测和分子外泌体，以监测多形胶质母细胞瘤（GBM）中的肿瘤进展和治疗反应。外泌体是由癌细胞积极脱落的膜结合的磷脂纳米层，该平台将用于确定血清中外泌体的抽象和组成。候选人Hyungsoon IM在开发具有工程背景背景的新敏感性平台方面拥有丰富的经验，现在旨在过渡到生物医学癌症研究。通过培训，他将进一步开发技能集，以进行独立的翻译研究，并为癌症外泌体研究领域做出重大贡献。这项工作将在马萨诸塞州综合医院和哈佛医学院的系统生物学中心根据Ralph Weissleder博士的心态进行。为了扩大专业知识，他还引入了Xandra Breakefield，他是国际公认的外泌体生物学专家和Antonio Chiocca教授，Antonio Chiocca是一位神经外科肿瘤学家，对转化工作感兴趣，以获得更多的心理和专业知识。咨询委员会的这些成员将支持Hyngsoon的工作向独特而独立的投资线过渡，并允许他发展成为独立的生物医学癌症研究员的成功职业。该研究计划旨在首先开发微阵列纳米质量外粒子灵敏度平台（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，但是它们的分子组成的数量尤其是在临床环境中挑战。从初步研究使用血浆纳米骨的初步研究中，将通过与最先进的纳米制动技术和高通量读取系统集成，从而开发出具有400个传感器阵列的高级NPLEX平台。在特定的目标2中，NPLEX平台将用于GBM小鼠模型中外泌体的串行分析。外泌体前后处理后的纵向评估将用于确定与肿瘤进展和治疗反应相关的特定外泌体标志物，以预测治疗效率。提出的平台将允许对肿瘤来源外泌体进行全面分析，以阐明原发性和转移性肿瘤的分子谱，并提供信息以指导有效的治疗方案。新的NPLE系统可能是促进癌症研究和临床实践的变革性工具。