Tunable Fluorescent Organic Nanoparticles for Cancer Imaging Applications

用于癌症成像应用的可调谐荧光有机纳米颗粒

基本信息

批准号：
9230752
负责人：
Aaron M. Mohs
金额：
$ 22.58万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-15 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9230752
关键词：
Address Advanced Malignant Neoplasm Apoptosis Biological Biological Process Cancer Biology Cancer Diagnostics Cells Chemical Structure Chemistry Color Complex Contrast Media Data Detection Development Dyes Early Diagnosis Elements Environment Epitopes Experimental Neoplasms Feasibility Studies Fluorescence Fluorescent Dyes Fluorescent Probes Goals Image Imaging Device Imaging technology Immune Inflammation Inflammatory Label Ligands Lymphatic Lymphatic vessel Malignant - descriptor Malignant Neoplasms Methods Modeling Multimodal Imaging Nerve Optics Performance Photobleaching Polymers Polysaccharides Population Process Property Proteins Quantum Dots Reagent Semiconductors Series Signal Transduction Surface Technology Testing Time Tumor Biology Tumor-Associated Process amphiphilicity anticancer research base bioimaging biomaterial compatibility cancer imaging cell type cellular imaging clinical application clinical development clinical diagnostics design experimental study flexibility fluorescence imaging fluorophore image guided intervention imaging agent imaging capabilities imaging platform imaging probe innovation insight molecular imaging monomer multimodality nanocrystal nanoparticle novel optical spectra polypeptide pre-clinical preclinical development quantum receptor self assembly small molecule success surface coating therapeutic evaluation three dimensional cell culture tumor tumor microenvironment tumorigenesis

项目摘要

PROJECT SUMMARY Fluorescent organic nanoparticles (FONPs) are a relatively new class of imaging probes that have unique potential for biomedical imaging applications because they integrate the synthetic flexibility of small organic molecules with the superior fluorescence properties of nanoparticles. FONPs have notable distinctions, however, compared to other types of fluorescent materials. Compared to the majority of organic dye fluorophores that display quenched fluorescence when aggregated, the fluorescent monomers that comprise FONPs have increased signal upon their self-assembly. Relative to other types of fluorescent NPs, such as quantum dots, FONPs have high quantum yield, can be optimized for size, color, and surface coating, and do not require the use of toxic elements. These factors taken together suggest that FONPs have great potential as a platform imaging technology. Indeed, FONPs have been used experimentally for tumor detection, apoptosis assessment, and cell tracking. Despite these early successes, significant innovations must be made to precisely control optical properties including wavelength and brightness, FONP self-assembly and overall size, and development of an easily adaptive surface coating for conjugation specific to the intended application. Thus, the overarching goal of this IMAT R21 proposal is to synthesize, characterize, and evaluate a new class of fluorescent organic nanoparticles (FONPs) as a novel imaging agents with controlled size, emission wavelengths, surface chemistry, and high quantum yield for diverse cancer imaging applications. Further, we hypothesize that FONPs with tunable fluorescence emission, size minimization, paramagnetic cores, and a clickable surface coating will provide targetable nanoparticle-based technology with bright and stable fluorescence emission for multiplexed and multimodality imaging. The goals, hypothesis, and innovation are addressed in two specific aims: (1) To design clickable, optically tuned, self-assembled fluorescent organic nanoparticles; (2) To validate the capacity of FONPs for multiplexed cellular imaging to differentiate inflammatory and tumor-associated neurolymphatic remodeling. Using neurolymphatic remodeling as the first application of the FONPs serves multiple purposes. It necessitates synthesizing distinct colors of FONPs for simultaneous imaging of more than one cell population, requires at least two types of “clickable” targeting ligands, and allows for a quantifiable comparison with fluorescent protein-labeled cells and ligands conjugated to either small organic dyes or QDs. Finally, the 2D, 3D, and ex vivo results obtained with this proposal will provide additional insight into distinguishing inflammation from tumorigenesis using FONPs as a platform technology. If the quantitative milestones of this IMAT R21 are achieved, it will directly support their continued preclinical and clinical development.

项目概要荧光有机纳米粒子（FONP）是一类相对较新的成像探针，具有独特的生物医学成像应用的潜力，因为它们集成了小型有机材料的合成灵活性然而，具有纳米颗粒优异荧光特性的分子具有显着的区别。与其他类型的荧光材料相比，与大多数有机染料荧光团相比。聚集时显示猝灭荧光，构成 FONP 的荧光单体具有相对于其他类型的荧光纳米粒子，例如量子点，其自组装信号增强。 FONP 具有高量子产率，可以针对尺寸、颜色和表面涂层进行优化，并且不需要这些因素综合起来表明 FONP 作为一个平台具有巨大的潜力。事实上，FONP 已在实验中用于肿瘤检测、细胞凋亡评估、尽管取得了这些早期的成功，但必须进行重大创新才能精确控制光学。特性，包括波长和亮度、FONP 自组装和整体尺寸，以及开发易于适应特定于预期应用的表面涂层。 IMAT R21 提案的目的是合成、表征和评估一类新型荧光有机材料纳米颗粒（FONP）作为一种新型成像剂，具有可控的尺寸、发射波长、表面化学、以及多种癌症成像应用的高量子产率。此外，我们还敢于采用 FONP。可调谐荧光发射、尺寸最小化、顺磁芯和可点击的表面涂层将提供基于靶向纳米颗粒的技术，具有明亮且稳定的荧光发射，用于多重检测目标、假设和创新有两个具体目标：(1) 设计可点击、光学调谐、自组装的荧光有机纳米粒子（2）验证容量； FONP 用于多重细胞成像以区分炎症和肿瘤相关神经淋巴管使用神经淋巴重塑作为 FONP 的第一个应用有多种用途。需要合成不同颜色的 FONP 以同时对多个细胞群进行成像，需要至少两种类型的“可点击”靶向配体，并允许与荧光蛋白标记的细胞和配体与小有机染料或量子点缀合最后，2D、3D、通过该提案获得的离体结果将为区分炎症和炎症提供更多见解如果 IMAT R21 的定量里程碑是使用 FONP 作为平台技术的肿瘤发生。一旦实现，它将直接支持他们持续的临床前和临床开发。