Vincent Pecoraro

From

University of Michigan - USA

In residence at

Molecular Biophysics Center (CBM) / CNRS - FR

Host scientist

Stéphane Petoud

PROJECT

Our objective is to prepare novel Near Infrared (NIR) emitting molecules that exploit the luminescence properties of lanthanides to serve as probes for biological systems. Metallacrowns will serve as platform as they are  a self-assembling class of molecules that possess superb luminescence properties, especially in the NIR. They can be prepared in large quantities and in high purity, an important advantage for biological optical imaging applications. They include sensitizing antenna and lanthanide emitters that allow for excellent emission. They are straightforwardly functionalized, allowing preparation of derivatives that can be solubilized, converted into dendrimers or allow attachment of chromophores or targeting groups. We will examine two general classes of metallacrowns in this work: LnZn16 and Ln­2Ga8 based systems. LnZn16 are excellent NIR emitting compounds that have been shown to distinguish necrotic cell death from apoptosis and living HeLa cells. In addition, these compounds can simultaneous stain and image HeLa cells. We are now modifying the ligands to shift the spectral signature from the UV/Near visible range to longer wavelength excitation to enhance compatibility with cell and small animal bioimaging. We have also functionalized these compounds with alkyne groups in order to place biotin, PEG or antibodies onto to the metallacrown. The majority of the work will be completed with Ln­2Ga8 metallacrowns. These species can sensitive both visible and NIR emission. Furthermore, we have recently learned that they are outstanding nanothermometers that can measure temperature between 150-350 K (with precision of 0.1 K in the physiologic range). These molecules have been converted into poly(amidoamine)  dendrimers that cross HeLa cell membranes and are incorporated into endosomes. Thus, this system can directly measure temperatures in cell compartments. Other modifications include attaching long wavelength antenna, biotin, peptide dendrons, BSA and antibodies. All of these complexes will be evaluated in HeLa cells to assess whether they will serve as probes of cell type and physical properties (e.g., temperature).