NIR-Emissive Polymersomal Markers for Molecula-Level Detection of Metastasis

用于分子水平转移检测的近红外发射聚合物标记物

基本信息

批准号：
7283176
负责人：
MICHAEL J THERIEN
金额：
$ 24.2万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2008-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7283176
关键词：
Adhesions Animal Model Animals Antibodies Benchmarking Binding Biocompatible Biological Biology Biomedical Engineering Blood Blood Vessels Butadiene Caliber Carcinoma Cell Adhesion Cell Count Cell surface Cells Chemicals Clinical Condition Confocal Microscopy Coupled Coupling Data Depth Detection Diagnosis Diagnostic Disease Disseminated Malignant Neoplasm Drug Delivery Systems Early Diagnosis Engineering Ethylene Oxide Evaluation Evolution Fab Immunoglobulins Family Flow Cytometry Fluorescence Foundations Generations Goals Head Image In Vitro Label Life Ligand Binding Localized Lung Malignant Neoplasms Measurable Measures Mechanics Mediating Medical Medicine Membrane Methods Microscopic Modeling Modification Molecular Mono-S NCI Unconventional Innovations Program Nanotechnology Nature Neoplasm Metastasis Normal Cell Numbers Optics Output Penetration Peptides Polymers Population Porphyrins Principal Investigator Procedures Property Proteins Protocols documentation Reaction Residual Tumors Signal Transduction Solutions Son Stream Structure Surface System Technology Testing Thick Time Tissue Model Tissues Tumor Tissue Vesicle Work antibody conjugate aqueous arteriole base bioimaging cancer cell caprolactone cellular targeting chemical property chemical synthesis chromophore clinically relevant copolymer design di-block copolymer engineering design fluorophore functional group in vivo in vivo Model insight member nano nanoscale neoplastic cell optical imaging physical property polyethylene oxide-polycaprolactone copolymer porphyrin structure programs prototype quantum receptor research study self assembly tissue culture tool tumor

项目摘要

DESCRIPTION (provided by applicant): The detection of early carcinoma or dormant or latent metastatic tumor cells remains an elusive but important clinical goal. We seek to develop further revolutionary new nanotechnology that enables optically based detection of metastatic cancer cells. Towards this goal, we will further refine design criteria for near infrared (NIR) emissive polymersomes, a promising new soft matter nanoscale platform for in vivo diagnostic and drug-delivery applications. This program will develop (i) targeted nanoscale (diameter < 100 nm) NIR- emissive polymersomes, (ii) nanoscale NIR-emissive polymersomes having optimized emissive output, (iii) prototype targeted nanoscale vesicles in which the polymeric building blocks are based-upon FDA-approved materials, (iv) targeted NIR-emissive polymersomes with ideal cell-surface adhesion dynamics, and (v) methods and technology that provide not only new insights into metastatic disease, but define an evolvable nanoscale platform for in vivo dormant tumor cell detection, diagnosis, and treatment. These efforts involve correlating NIR fluorophore structure and photophysics, polymersome composition of matter, vesicle mechanical and biological properties, nanoscale NIR-emissive polymersome fluorescence output, and the nature of the cellular targeting motif, with in vivo function and efficacy. As such, the experimental approach we pursue is cross-cutting and integrative, encompassing supramolecular chemical synthesis, photophysical characterization, in vivo imaging, bioengineering, biology, and medicine. We will strive to establish design principles that will ultimately enable real-time detection and identification of limited target cell numbers under clinically relevant diagnostic conditions, and define new tools for the study of metastatic disease.

描述（由申请人提供）：早期癌或休眠或潜伏转移性肿瘤细胞的检测仍然是一个难以捉摸但重要的临床目标。我们寻求开发进一步革命性的新型纳米技术，以实现基于光学的转移性癌细胞检测。为了实现这一目标，我们将进一步完善近红外（NIR）发射聚合物囊泡的设计标准，这是一种用于体内诊断和药物输送应用的有前景的新型软物质纳米级平台。该计划将开发 (i) 目标纳米级（直径 < 100 nm）NIR 发射聚合物囊泡，(ii) 具有优化发射输出的纳米级 NIR 发射聚合物囊泡，(iii) 原型目标纳米级囊泡，其中聚合物构件基于该囊泡FDA 批准的材料，(iv) 具有理想细胞表面粘附动力学的靶向近红外发射聚合物囊泡，以及 (v) 不仅提供新见解的方法和技术转移性疾病，但定义了一个可进化的纳米级平台，用于体内休眠肿瘤细胞的检测、诊断和治疗。这些工作涉及将近红外荧光团结构和光物理学、聚合物囊泡物质组成、囊泡机械和生物特性、纳米级近红外发射聚合物囊泡荧光输出以及细胞靶向基序的性质与体内功能和功效相关联。因此，我们追求的实验方法是交叉和综合的，涵盖超分子化学合成、光物理表征、体内成像、生物工程、生物学和医学。我们将努力建立设计原则，最终能够在临床相关诊断条件下实时检测和识别有限的靶细胞数量，并定义用于研究转移性疾病的新工具。