6533b86dfe1ef96bd12ca5b2

RESEARCH PRODUCT

Development of functionalizable azaBODIPYs for the conception of theranostic agents and bimodal probes for imaging uses

subject

description

The in vivo use of optical imaging is still limited by the lack of near infrared emitting probes. This thesis work focuses on the optimization and valorization of a water-soluble fluorescent platform whose optical properties enable an in vivo use. Two distinct applications were investigated for this WazaBY (Water-soluble azaBODIPY) platform: use as a PET (or SPECT) / optical bimodal probe, and as a theranostic agent. Concerning the first project, we were able to develop a targetted SPECT/optical bimodal probe, which was radiometallated with indium 111. Using xenografted murine models, we were able to show a clear accumulation of the probe in the tumor 24 hours after injection. Moreover, the probe was validated as a contrast agent for fluorescence guided surgery experiment. The second project of this thesis began by the synthesis of a first generation of gold based theranostic agents. The goal was to develop a new therapeutic complex, which can be tracked in vitro and in vivo thanks to optical imaging. In vitro preliminary results showed that the theranostics displayed a cytotoxicity comparable to auranofin on the tested cell lines (4T1, MDA MB 231, CT26 and SW480). A second part of this project focused on the develoment of « smart » probes for a theranostic use. Those probes are designed to undergo photophysical properties changes, when their metallic centre, responsible for the therapeutic role, is released. Two molecules were synthesized, both displaying an on/off behavior.