Grant: CIHR Fellowship

Decades of cancer research have turned deadly diseases into manageable conditions. Unfortunately, such achievements have not been the case for all types of cancers. Despite new advances, the treatment of advanced solid tumors remains limited. One such challenge comes from solid tumors being surrounded by a tight matrix composed of collagens. This physical barrier protects tumors by limiting drug accessibility and immune infiltration. The question arises, however, whether this matrix may be used to target drugs and RNAs to tumors. Indeed, the delivery of RNA molecules directly into tumors could provide a new strategy to fight cancer. RNA molecules were shown to achieve anti-cancer activity by blocking processes important for growth. They can also help by recovering the function of disrupted or mutated genes. Our laboratory currently works on the development of new lipid nanoparticles (LNPs) for RNA delivery to remote organs. In this proposal, we aim to use this expertise to develop the first set of matrix-anchoring lipid nanoparticles (MAG-LNPs) that can deliver RNAs to solid tumors. To identify those formulations, we will screen a large library of MAG-LNPs in cancer-bearing mice. Each set of these MAG-LNPs will have slight chemical modifications that will impact their distribution in the body. We will also add collagen-binding molecules to some MAG-LNPs to increase their interaction with the tumor's matrix. For the screen, the MAG-LNPs will contain a specific DNA barcode. This barcode will allow us to identify each formulation after the screen and reveal the most potent MAG-LNPs. Afterward, we will study the efficacy of these MAG-LNPs by loading them with therapeutic RNAs capable of stopping cancer growth. MAG-LNPs could thus provide a versatile platform for personalized cancer and gene therapy. This technology would also represent a significant leap in our capacity to identify new genetic targets for cancer treatment.