John Trant – 2020 Feature Grant Recipient
Generously Funded by the Liedtke MetaLab Research Fund
John Trant – University of Windsor
Project Title: “A universal drug delivery vehicle to transport drugs across the blood-brain barrier to target Glioblastoma”
Description of Project:
Glioblastoma (GBM) has a five-year survival under 7 per cent. Surgery and radiation remain the standard of care for patients with these cancers, with chemotherapies playing primarily a supporting role, despite so many drugs showing remarkable benefits in cell models.
One big reason for this are the physiochemical limitations that prevent anti-cancer drugs from both crossing the blood-brain barrier (BBB) and then remaining in the brain. Imagine what would be possible for these patients if we could courier these drugs right to the cancer cells through the BBB.
Ideally, we would have a universal drug delivery vehicle that could simply have different “addresses” (biomarkers specific for given cell surface receptors) attached to it, so once in the brain it goes to only cancer cells. Even better would be a capsule that does not degrade until it enters the target cell where it then tracelessly disintegrates without consequence.
This is precisely the technology we are designing in the Trant Lab: triggerable (i.e. by light, heat, enzymes) polymer nanocapsules that are suitable for crossing the BBB and localizing only to specific cells expressing certain surface markers. This project proposes to show that we can use these to cross a model BBB in zebrafish.
What receiving this award means:
This funding allows us to focus on this project and really push it forward as we have been operating it with residual funds from our general purpose research funds, so this greatly accelerates our research. We hope, that by the end of the funding period, and with these resources, we will have a proof-of-concept model and sufficient preliminary data to convert your support into a much larger continuing fund from an industrial partner or the Canadian or US national funding bodies. But this would not be possible without the initial support from Brain Tumour Foundation of Canada.
Final Report: May 2022
The generous grant from the Brain Tumour Foundation and Liedtke MetaLab Research Fund was provided to support our development of a Universal Tunable, Targetable, Self-Immolative NanoCapsule to penetrate the brain and deliver a cargo such as drugs targeting glioblastoma multiforme to the brain. One major problem with brain cancer is it is hard to get effective drugs into the brain, and then hard to get them specifically to cancer cells. Our idea here is that it is possible to package these drugs into parcels that only release their cargo when they reach their final destination, at which point the packaging disappears completely into amino acids. With the funding from the Foundation we were able to add peptides that assist translation across the blood-brain-barrier to our nanocapsule polymers. These bind the right proteins to help “Trojan Horse” the drug and the carrier across the blood brain barrier without prematurely releasing the drug in the simulated blood stream. Next steps in the coming years will be to test these systems in animal models and demonstrate that they work well in the more complex in vivo environment. The funding from the Foundation has provided the required basic data we need to acquire additional funding from multi-year support grants and has allowed us to show that this idea is feasible. We would like to thank Liedtke MetaLab Research Fund for supporting science and the training of students in Windsor-Essex.