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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：
9078198
负责人：
RALPH WEISSLEDER, MD, PHD
金额：
$ 39.12万
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/9078198
关键词：
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 Human Image Immunocompetent Leukocytes Ligands Malignant Neoplasms Malignant neoplasm of ovary Measurement Measures Mesothelial Cell Messenger RNA Methods Modeling Molecular Monitor Mus Nanotechnology Noise Outcome Parents Patients Pharmaceutical Preparations Printing Process Protein Analysis Proteins RNA Reading Research Design 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 exosome improved innovation insight lithography macrophage method development mouse model nano nanocoating 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 research study response scale up sensor 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.