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

氟介导的 J 聚集作为明亮的近红外目标特异性成像剂

• 批准号: 8666545
• 负责人: Ellen May Sletten
• 金额: $ 4.92万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2014-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8666545
• 关键词: Award; Basic Science; Binding; Biodistribution; Biological; Biological Assay; Cancerous; Cell Culture Techniques; Cells; Chemistry; Disease; Dyes; Early Diagnosis; Electromagnetics; Endocytosis; Engineering; Extinction (Psychology); Glomerulonephritis; Goals; Green Fluorescent Proteins; Hydrophobic Interactions; Image; In Vitro; Light; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Mediating; Methods; Microscopy; Organism; Pathway interactions; Preparation; Prize; Property; Proteins; Quantum Dots; Research; Research Training; Risk; Serum; Technology; Transition Elements; absorption; base; biological systems; chromophore; cost; cytotoxicity; design; fluorophore; in vivo; light scattering; molecular imaging; nanoparticle; novel; optical imaging; public health relevance; quantum; receptor mediated endocytosis; research study; squaraine; success; tool

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.

描述（由申请人提供）：光学成像已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，这是2008年因荧光蛋白授予的贵族化学奖的例证。尽管取得了成功，但由于光散射和内源性分子的自动荧光并发症，体内的光学成像并不那么普遍。为了增加体内光学成像的效用，电磁光谱的近红外（NIR）区域中具有较大灭绝系数的灭绝系数和高量子产量是必不可少的。最近，由于量子点的有利的光物理特性，已经集中精力集中在量子点上。但是，量子点很大，由潜在的有毒过渡金属组成。因此，能够有效吸收并发出光的新有机材料至关重要。我的目的是设计具有与量子点相当的有机材料，并使用该材料进行前列腺癌的体内成像。该材料将基于常见有机荧光团的特定聚集（J-聚集），并且只有在发生癌细胞内的内吞作用时才会进行设计才能进行。 J聚集是获得净过渡偶极子的发色团对齐的，并导致与单体发色体相比，具有较大的灭绝系数ATA aTA aTA波长的bathoch骨移动。此外，J-聚集体具有接近统一的量子发射产率。这些特性是体内成像的理想选择，但是尚未用于分子成像的J凝聚物，这很可能是因为很难控制发色团与J聚集酸盐的对齐。我计划通过荧光和疏水相互作用的结合来克服这一挑战。该提案的具体目的是（1）通过荧光相互作用来控制正方形染料的J-聚集，（2）在体外开发和分析智能半氟糖染料J-聚集剂，（3）对智能半氟氟糖染料进行优化和使用，以在Vivo In Vivo In In In Vivo Interep中进行智能半氟化的Squaraine染料。