Fluorous mediated J aggregation as a bright NIR target specific imaging agent

描述(申请人提供)：光学成像使基础科学研究发生了革命性的变化，现在是研究生物途径的重要工具，2008年诺贝尔化学奖因荧光蛋白质而获奖就是例证。尽管取得了这一成功，但由于内源性分子的光散射和自身荧光的并发症，光学成像在体内的使用并不普遍。为了提高体内光学成像的实用性，在电磁光谱的近红外区具有大的吸收消光系数和高的发射量子产率的材料是必不可少的。近年来，由于量子点具有良好的光物理性质，人们对其进行了大量的研究；然而，量子点很大，并且由潜在的有毒过渡金属组成。因此，能够高效地吸收和发射近红外波长的光的新型有机材料是必不可少的。我的目标是设计一种具有与量子点相当的发射和吸收性能的有机材料，并将这种材料用于前列腺癌的体内成像。这种材料将基于常见有机荧光团的特定聚集(J-聚集)，并将被设计为仅在癌细胞内发生内吞作用时发生。J-聚集是生色团的排列，从而获得净的跃迁偶极子，并导致与单体生色团相比波长偏移的消光系数较大的材料。此外，J-聚集体的量子发射产额接近1。这些性质对于活体成像来说是理想的，然而J-聚集体还没有被用于分子成像，很可能是因为发色团到J-聚集体的排列很难控制。我计划利用憎氟和疏水相互作用的组合来克服这一挑战。这项建议的具体目的是：(1)通过氟相互作用控制方酸染料的J-聚集；(2)体外开发和检测智能半氟方酸染料J-聚集剂；(3)优化和应用智能半氟方酸染料用于体内靶向成像。 与公共健康相关：光学成像有望成为一种低成本、无毒、高灵敏度的疾病早期检测技术，如果有明亮的近红外有机荧光团可用的话。我的目标是通过设计一种新的材料，通过常见有机荧光团的特殊聚集(J-聚集)来设计一种新的靶标激活成像材料，从而提高体内光学成像的灵敏度。J-聚集将通过憎氟和疏水相互作用来调节，并产生在电磁光谱的近红外区域具有接近1的吸收和发射量子产率的大消光系数的材料。

DESCRIPTION (provided by applicant): Optical imaging has revolutionized basic science research and is now an essential tool for studying biological pathways, as exemplified by the 2008 Noble Prize in Chemistry awarded for fluorescent proteins. Despite this success, the use of optical imaging in vivo is not as prevalent due to complications from light scattering and autofluorescence of endogenous molecules. In order to increase the utility of optical imaging in vivo, materials that have large extinction coefficients for absorption and high quantum yields of emission in the near infrared (NIR) region of the electromagnetic spectrum are essential. Recently, much effort has been focused on quantum dots due to their advantageous photophysical properties; however, quantum dots are large and composed of potentially toxic transition metals. Thus, new organic materials that are able to efficiently absorb and emit light a NIR wavelengths are essential. I aim to engineer an organic material that has emission and absorption properties comparable to quantum dots and use this material for in vivo imaging of prostate cancer. This material will be based off the specific aggregation (J-aggregation) of common organic fluorophores, and will be engineered to take place only when endocytosis within a cancerous cell occurs. J-aggregation is the alignment of chromophores such that a net transition dipole is obtained, and results in a material that has a large extinction coefficient ata wavelength bathochromically shifted compared to the monomeric chromophore. Additionally, J- aggregates have quantum yields of emission that approach unity. These properties are ideal for in vivo imaging, yet J-aggregates have not been employed for molecular imaging, most likely because the alignment of chromophores into a J-aggregate is difficult to control. I plan to overcome this challenge using a combination of fluorophobic and hydrophobic interactions. The specific aims of this proposal are to (1) control J-aggregation of squaraine dyes through fluorous interactions, (2) develop and assay smart semi-fluorinated squaraine dye J- aggregators in vitro, and (3) optimize and employ the smart semi-fluorinated squaraine dyes for targeted in vivo imaging. PUBLIC HEALTH RELEVANCE: Optical imaging is poised to be a low-cost, non-toxic, highly sensitive technology for the early detection of disease if bright, near-infrared, organic fluorophores are available. I aim to increase the sensitivity of optical imaging in vivo by engineering a novel material for target-activated imaging through the specific aggregation (J-aggregation) of common organic fluorophores. The J-aggregation will be mediated by fluorophobic and hydrophobic interactions and yield a material with large extinction coefficients of absorption and quantum yields of emission that approach unity in the near-infrared region of the electromagnetic spectrum.