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.
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.
|Zarzar, Lauren D; Sresht, Vishnu; Sletten, Ellen M et al. (2015) Dynamically reconfigurable complex emulsions via tunable interfacial tensions. Nature 518:520-4|