Fluorescence and photoacoustic (PA) imaging are both powerful tools for visualization of biological tissues and organs in non-invasive ways. However, these technologies are limited by the lack of efficient contrast agents. NIR light (650-900 nm) with relatively low absorption and scattering in organisms allows for deeper in vivo imaging, lower auto-fluorescence as well as a good signal to noise ratio. Hence, design and synthesis of efficient NIR organic dyes are of great significance for fluorescence or PA bio-imaging. Meanwhile, encapsulation of organic dyes in nanoparticles dispersible in water present great potential in bio-optical imaging, offering the advantages of high brightness, good photo-stability, excellent biocompatibility and potential targeting ability, etc. Our main goal in this thesis is to synthesize novel organic contrast agents for in vivo fluorescence or PA imaging.
In the first part of our work, we synthesized and studied the spectroscopic properties of two series of new NIR-emitting dyes CBZ1-CBZ8 and EBTN1-EBTN5 based on a push-pull D-π-A scaffold. EBTN1-EBTN5 using bithiophenepyrrole as the conjugated π bridge showed much red-shifted optical properties in comparison to CBZ1-CBZ8 dyes based on fluorene. Among all these dyes, EBTN4 is of the most red-shifted absorption and emission while keeping very impressive quantum yield (λabs/λemi=665/885 nm, Φf=33% in toluene). Fluorescent micelle/silica NPs (SiNPs) in which the synthesized organic dyes are encapsulated in amphiphilic polymer Pluronic F127 were then prepared for improving the dyes’ water-solubility. EBTN4 SiNPs with the most red-shifted absorption and emission (λabs/λemi=680/810 nm, Φf=12% in water) coming along with the monodispersed size around 22 nm are very promising for fluorescence bioimaging. SiNPs functionalized by different moieties on their surface were also prepared.
In parallel, we studied different strategies to maximize the dye loading capacity of NPs (micelle/silica NPs and polymer NPs) for in vivo PA imaging, as this technic requires very high dye concentration. We first tried to graft NIR-absorbing hemicyanine dyes on the SiNPs surface. Then three kinds of polymer NPs were obtained using the same dyes in collaboration with Institute des Matériaux Polymères (IMP).
Finally, in the third part of our work, we studied the sensing behavior of dicyanovinyl containing dyes PTTCN and EBTN1 for primary amine. Based on ICT mechanism, PTTCN and EBTN1 all presented immediate color change along with fluorescence “turn-on” responses (1311-fold fluorescence enhancement for PTTCN) to primary amine with high sensitivity and selectivity in solution. PTTCN sol-gel film was prepared to detect primary amine vapor in colorimetric way (emission shifted from 720 nm (φ=23%) to 500 nm (φ=43%)). In order to take advantage of the reversibility of the reaction, EBTN1 glass slide was preliminarily prepared and tried for circle detection of primary amine vapor.