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

描述（由申请人提供）：光学成像已经彻底改变了基础科学研究，现在是研究生物途径的重要工具，2008年诺贝尔化学奖授予荧光蛋白就是一个例子。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，在体内使用光学成像并不普遍。为了提高体内光学成像的效用，在电磁波谱的近红外（NIR）区域具有大的吸收消光系数和高发射量子产率的材料是必不可少的。近年来，量子点由于其优越的光物理特性而受到广泛关注；然而，量子点很大，并且由潜在有毒的过渡金属组成。因此，能够有效吸收和发射近红外波长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媲美的发射和吸收特性的有机材料，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），并且将被设计为仅在癌细胞内吞作用发生时才发生。j聚集是指发色团的排列，从而获得净跃迁偶极子，并且与单体发色团相比，在波长上有较大的消光系数。此外，J-聚集体的发射量子产额接近统一。这些特性是体内成像的理想选择，但j聚集体尚未用于分子成像，很可能是因为发色团与j聚集体的排列难以控制。我计划利用憎氟和疏水相互作用的结合来克服这一挑战。本提案的具体目标是：(1)通过氟相互作用控制方卡因染料的J聚集，(2)在体外开发和测定智能半氟化方卡因染料J聚集物，以及(3)优化和使用智能半氟化方卡因染料进行靶向体内成像。

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.