Head of the Lipid Nanoparticles platform

In my PhD thesis, I aim to establish novel self-assembling dendrimer nanosystems using positron emission tomography (PET) imaging for tumor detection.The first part focused on developing amphiphilic dendrimers to study the impact of hydrophobic/hydrophilic balance on biodistribution. New dendrimers incorporating fluorinated motifs and enlarged hydrophobic entities showed promising results, with one fluorinated dendrimer exhibiting superior tumor imaging. The hydrophobic part of amphiphilic dendrimers significantly influenced self-assembly and biodistribution, offering insights for designing precise imaging agents.In the second part, I explored co-assembling strategies to create modular nanotracers with active targeting motifs for tumor PET imaging. Amphiphilic dendrimers bearing mannose terminals, peptide ligands were synthesized for targeting specific receptors on cancer cells. Nanotracers combining targeting ligands and imaging dendrimers were constructed via co-assembly, showing small size, stability in serum, and effective targeting of receptors and cells in vitro and in vivo.These studies illustrate the potential of self-assembling dendrimer nanosystems for developing nanoprobes in bioimaging. The modular nature of self-assembly allows flexibility in constructing diverse nanoprobes for specific applications, enabling precision and personalized medicine. Moreover, the established dendrimer concept can extend to create nanoprobes for multimodal imaging and theranostics, advancing precision medicine and personalized treatment.

Synthesis and characterization of radiosensitizer gold nanoparticles (GNPs) grafted with polymer corona for radiotherapy treatment.During these six months, my project was to expand the range of polymer corona of the NPs by varying the length of the chains, but also their chemical nature. Thereafter thanks to these polymers, I synthesized the GNPs. Finally, I performed in vitro assays to evaluate the toxicity of the GNPs, but also their ability to penetrate inside the cells.I synthesized the polymers by ATRP and characterized by 1H NMR, FT-IR and SEC/MALS. Then, I synthesized the GNPs by reduction of gold salts in presence of polymers and characterized them by UV-Visible, TGA, ICP-MS, and TEM. Finally, I carried out MTT assay to determine the cytotoxicity. Lastly, I performed cell internalization assay to quantify the number of nanoparticles internalized by the cells. The tumor cells were incubated for a given time in the presence of GNPs, then, I achieved ICP-MS measurements to determine the amount of gold present in the cells.

Characterisation of gold nanoparticles impact on phospholipids membraneI used phospholipids to mimic the cell membranes. Our strategy to replicate the cell membrane is to use two forms of phospholipid assemblies: planar bilayer and the liposomes. Firstly I performed dynamic light scattering to see how the GNPs affect the size of the liposomes. Then I anchored the liposomes on a gold wafer to form a planar bilayer, in order to carry out Electrochemical Impedance Spectroscopy measurements (EIS). I followed the fusion and deposition of the vesicle by measuring the thickness on the gold wafer using ellipsometry measurement. Finally I achieved EIS measurements to analyse the influence of GNPs on the shape of phospholipids bilayer. I fitted and modelled the data by an equivalent electric circuit (EEC) to obtain more accurate information about the system.