6533b836fe1ef96bd12a115a

RESEARCH PRODUCT

Multifunctional platforms for cancer theranosis

subject

description

The objective of this thesis was to develop multifunctional tools for cancer theranosis, particularly based on nanotechnology. The work is based on the premise of monomolecular multimodal platform that aims to create the building blocks that can be used for the synthesis of functionalized nanoparticles, bioconjugates or targeted small molecular imaging probes.The initial work focused on the synthesis of the chelator based silane precursors. These novel precursors were employed for the functionalization of AGuIX nanoparticles and have also been implicated in a one pot AGuIX synthesis. Radiolabelling of these nanoparticles was performed with the aim to evaluate the stability of these nanoparticles under physiological conditions. Furthermore, these nanoparticles were investigated in TSA tumor model in order to evaluate their pharmacokinetics, biodistribution behaviour and value in PET-MRI imaging.In the second part of the work, building blocks/ligands have been developed and successfully deployed for the functionalization of gold nanoparticles. Multimodal ligands containing different combinations of chelators, targeting moieties, functional groups and dyes were synthesized. Gold nanoparticles for PET-MRI and PSMA targeting SPECT imaging were further radiolabeled (64Cu/111In) and showed excellent stability. PSMA targeting ligand exhibited good affinity towards PSMA, whereas the in vivo studies of the gold nanoparticles for PET-MRI in TSA tumor model demonstrated good pharmacokinetics properties, underscoring their potential in cancer imaging and radiotherapy.The latter half of the thesis work focusses on the development of PET-Optical probes for PSMA positive cancer targeting imaging using small molecular probes, and for bioconjugation to antibody fragments and nanoparticles. A PSMA targeting probe based on NODAGA and IR-783 dye has been developed and characterized for its affinity, photophysical and radiolabelling properties. Likewise, a similar probe bearing a maleimide handle has been successfully used for the site-specific labelling of trastuzumab Fab’ fragments and functionalization of AGuIX nanoparticles. These bioconjugates and the nanoparticles have been thoroughly characterized and evaluated in relevant biological models to highlight their value in cancer theranosis.