Grant: CIHR Fellowship

Through evolution, bacterias have found various ways to circumvent the human defence mechanisms. One recent discovery in microbiology involves a pathogen that recruits host proteins on its surface to imitate healthy cells and avoid detection by the immune system. This project proposes to use the same approach to prolong circulation times of therapeutic nanocarriers (NC) in the blood, and enhance their efficiency to treat cancer. NC are particularly promising in cancer treatment because they are multifunctional; they can be loaded with multiple actives, can specifically target diseased cells and can elude resistance mechanisms which develop in cancer cells. However, their efficiency is limited by rapid clearance from the bloodstream and non-specific sequestration in the liver and spleen. In this project, the surface of NC will be functionalized with recognition patterns for host proteins implicated in the discrimination between "self" and "non-self". Upon injection of the NC, the ligand will sheath their surface by binding its target in the plasma, and protect it from recognition by the traditional defence mechanisms. Using state-of-the-art ligand synthesis techniques to mimic this bacteria-inspired mechanism will translate into less capture in the liver and the spleen, and higher doses delivered to the diseased cells. During this project the candidate will synthesize the ligand, attach it to the surface of NC and study its ability to prolong the NC circulation time in the bloodstream. Lastly, the ability of drug-loaded NC to induce tumour regression will be evaluated. The results obtained in this work will result in better fundamental understanding of one of the challenges faced in contemporary chemotherapy and nanomedicine. We believe these innovative ligands will allow the improvement of a variety of drug delivery systems, and open the door to the development of a number of other applications in tissue engineering and immunology.