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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：
7477325
负责人：
MICHAEL J THERIEN
金额：
$ 28.66万
依托单位：
DUKE UNIVERSITY
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 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7477325
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)：检测早期癌症或潜伏或潜伏的转移肿瘤细胞仍然是一个难以捉摸但重要的临床目标。我们寻求进一步开发革命性的新纳米技术，使基于光学的检测转移的癌细胞成为可能。为了实现这一目标，我们将进一步完善近红外(NIR)发射聚合体的设计标准，这是一种很有前途的新的软物质纳米级平台，用于体内诊断和药物输送应用。该计划将开发(I)靶向纳米级(直径100 nm)近红外发射聚合体，(Ii)具有优化发射输出的纳米级近红外发射聚合体，(Iii)其中聚合构建块基于FDA批准的材料的靶向纳米囊泡，(Iv)具有理想细胞表面黏附动力学的靶向近红外发射聚合体，以及(V)不仅为转移疾病提供新的见解，而且定义了用于体内潜伏肿瘤细胞检测、诊断和治疗的可进化纳米级平台的方法和技术。这些努力包括近红外荧光团结构和光物理、物质的聚合体组成、囊泡的机械和生物学特性、纳米尺度的近红外发射聚合体荧光输出以及细胞靶向基序的性质与体内功能和有效性的关联。因此，我们追求的实验方法是交叉和综合的，包括超分子化学合成、光物理表征、活体成像、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的诊断条件下实时检测和识别有限的靶细胞数量，并为转移疾病的研究定义新的工具。