Tunable Fluorescent Organic Nanoparticles for Cancer Imaging Applications

项目总结 荧光有机纳米粒子(FONPs)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化合物的合成灵活性 分子具有优越的纳米颗粒的荧光特性。然而，FONP有显著的区别， 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， 显示猝灭的荧光当聚集时，组成FONP的荧光单体具有 增强了它们自我组装的信号。相对于其他类型的荧光NPs，例如量子点， FONP具有高量子产率，可以针对大小、颜色和表面涂层进行优化，并且不需要 使用有毒元素。这些因素综合起来表明，FONPs作为一个平台具有巨大的潜力 成像技术。事实上，FONPs已经被实验性地用于肿瘤检测、细胞凋亡评估、 和手机追踪。尽管取得了这些早期的成功，但必须做出重大创新来精确控制光学 性质，包括波长和亮度，FONP自组装和整体尺寸，以及一种 易于适应的表面涂层，用于特定于预期应用的共轭。因此，首要目标是 这个IMAT R21提案的目的是合成、表征和评价一类新的荧光有机化合物 纳米颗粒(FONPs)作为一种新型的显像剂，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额。此外，我们假设FONPs与 可调的荧光发射、尺寸最小化、顺磁磁芯和可点击的表面涂层将 为多路复用提供具有明亮和稳定荧光发射的靶向纳米颗粒技术 和多模式成像。目标、假设和创新有两个具体目标：(1) 设计可点击、光学可调、自组装的荧光有机纳米粒子；(2)验证容量 FONPs用于多重细胞成像鉴别炎性和肿瘤相关神经淋巴管 改建。使用神经淋巴重塑作为FONPs的第一个应用具有多个目的。它 需要合成不同颜色的FONP以同时对多于一个的细胞群体进行成像， 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连接到小的有机染料或量子点。最后，2D、3D、 通过这一提议获得的体外结果将为区分炎症和 以FONPs为平台技术的肿瘤发生。如果这款IMAT R21的量化里程碑是 一旦实现，它将直接支持他们持续的临床前和临床发展。

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.