Therapeutic particles targeting to induce autophagy as a tumor and neurodegeneration suppressor
The goal of this project is to develop and characterize safe biodegradable particles, vectorising immune-modulators able to induce autophagy and targeting liver to act as tumour suppressor in the context of chronic liver diseases or other cancers. Indeed, some evidence suggests that autophagy may serve as a tumour suppressor in cases of chronic liver disease and liver cirrhosis. Furthermore, Adjuvatis produce, develop and characterize biodegradable and safe-by-design i-Partiles® made of poly(lactic acid), a biodegradable polymer. Those particles can be formulated with active pharmaceutical ingredients by encapsulation within their polymeric core and/or by absorption at their surface. We recently published that these i-Particles containing an encapsulated NOD agonist to induce autophagy in vitro. Finally, some preliminary data highlight that those particles spontaneously target the liver after their intravenous administration.
The PhD student will perform three main tasks. The first will be to formulate TLR/NOD ligands with the i-Particles and then characterize them. Autophagy efficacy of TLR/NOD ligands will be evaluated under soluble and particulate forms using mammalian reporter cell lines and human dendritic cells prepared from monocytes in vitro. The second task will be to perform a biodistribution study and pharmacokinetic monitoring in mice of fluorescent i-Particles (in presence or absence of TLR/NOD ligands) using whole imaging tools, after their administration. The third and final task will be the evaluation of therapeutic efficacy of the active particles selected in WP1 and 2, using in vivo mouse models available in the consortium such as LBTI (Verrier’s group, France) or Kirkin and Jungbluth groups (UK).