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: 8455133
• 负责人: Ellen May Sletten
• 金额: $ 4.71万
• 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/8455133
• 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; 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. 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.

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证。尽管取得了这一成功，但由于内源性分子的光散射和自发荧光的并发症，体内光学成像的使用并不普遍。为了提高体内光学成像的实用性，在电磁波谱的近红外（NIR）区域中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，由于量子点具有优越的物理化学性质，人们对量子点进行了大量的研究;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NIR波长的光的新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异性聚集（J-聚集），并且将被设计为仅在癌细胞内发生内吞作用时发生。J-聚集是发色团的排列，使得获得净跃迁偶极，并且导致与单体发色团相比在波长红移时具有大消光系数的材料。此外，J-聚集体具有接近1的发射量子产率。这些性质对于体内成像是理想的，但J-聚集体尚未用于分子成像，最有可能是因为发色团排列成J-聚集体难以控制。我计划使用疏氟和疏水相互作用的组合来克服这一挑战。该提议的具体目的是（1）通过氟相互作用控制方酸菁染料的J-聚集，（2）在体外开发和测定智能半氟化方酸菁染料J-聚集剂，以及（3）优化和使用智能半氟化方酸菁染料用于靶向体内成像。 公共卫生相关性：光学成像有望成为一种低成本，无毒，高灵敏度的技术，用于早期发现疾病，如果明亮的，近红外，有机荧光团可用。我的目标是增加体内光学成像的灵敏度，通过工程一种新的材料，通过特定的聚集（J-聚集）的常见有机荧光团的目标激活成像。J-聚集将通过疏氟和疏水相互作用介导，并产生具有大的吸收消光系数和发射量子产率的材料，其在电磁光谱的近红外区域中接近统一。