Tunable Fluorescent Organic Nanoparticles for Cancer Imaging Applications

项目摘要 荧光有机纳米颗粒（FONP）是一类相对较新的成像探针，其具有独特的光学特性。 潜在的生物医学成像应用，因为它们集成了小的有机合成的灵活性， 具有纳米颗粒的上级荧光性质的分子。然而，FONP有明显的区别， 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， 当聚集时显示淬灭的荧光，包含FONP的荧光单体具有 增强了自我组装的信号。相对于其他类型的荧光NP，例如量子点， 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，并且不需要使用纳米粒子。 使用有毒元素。这些因素综合起来表明，FONP作为一个平台具有巨大的潜力 成像技术事实上，FONP已在实验上用于肿瘤检测、凋亡评估， 和手机追踪尽管这些早期的成功，重要的创新必须作出精确控制光学 包括波长和亮度，FONP自组装和整体尺寸的特性，以及 易于适应的表面涂层，用于特定于预期应用的结合。因此，总体目标 该IMAT R21提案的一个主要目的是合成、表征和评估一类新的荧光有机化合物， 纳米颗粒（FONP）作为一种新型的成像剂，具有可控的尺寸、发射波长、表面化学， 以及用于多种癌症成像应用的高量子产率。此外，我们假设FONP与 可调荧光发射、尺寸最小化、顺磁性核心和可点击的表面涂层将 提供基于靶向纳米颗粒的技术，具有明亮和稳定的荧光发射， 和多模态成像。目标、假设和创新在两个具体目标中得到解决：（1） 设计可点击的、光学调谐的、自组装的荧光有机纳米粒子;（2）验证 FONP用于多重细胞成像以区分炎症和肿瘤相关的神经淋巴 重塑使用神经淋巴重塑作为FONP的第一个应用服务于多个目的。它 需要合成不同颜色的FONP用于同时成像多于一个细胞群， 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与小的有机染料或QD缀合的配体。最后，2D，3D， 并且用该提议获得的离体结果将提供区分炎症与 使用FONP作为平台技术的肿瘤发生。如果本IMAT R21的定量里程碑是 这将直接支持其持续的临床前和临床开发。

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.