Monday, April 28, 2025
4/28/2025
Targeting platinum(IV) prodrug to GBM tumors using a brevican-binding peptide - Project Summary/Abstract Despite recent progress in cancer therapy, the brain tumor glioblastoma (GBM) remains an extremely challenging disease and new therapies are much needed. One of the biggest obstacles to effective treatment of GBM is the presence of the blood-brain barrier (BBB), which prevents the passage of most drugs into the brain. The highly invasive nature of GBM means there are always cells that remain after surgery in otherwise normal brain tissue, and these cells are protected behind the BBB, preventing many therapeutics from reaching them. To address this, we have formed a collaboration between Cho’s pre-clinical GBM therapeutics group at BWH (PI), and Pentelute’s peptide chemistry group at MIT (Co-I) to develop a new therapeutics to 1) specifically target GBM cells, and 2) cross the BBB. Our collaboration has identified a novel peptide, called BTP-7 that can specifically target GBM cells and penetrate the BBB, serving as a promising agent to deliver potent anti-cancer drugs to the tumor. The Pt(IV) drug has widespread clinical use for cancer treatment, but it is unable to cross the BBB, leading to low brain uptake and limiting its effectiveness for treating GBM. Here, we propose to attach Pt(IV) to BTP-7 (Pt(IV)-BTP-7), with the aim to increase Pt(IV) drug delivery to intracranial GBM tumors. Our specific aims (SA) are as follows: SA 1. Analyze Pt(IV)-BTP-7 specificity to dg-Bcan and potential to cross the BBB in vitro. SA 2. Investigate the biodistribution (BD), pharmacokinetics (PK) and pharmacodynamics (PD) of Pt(IV)-BTP-7 in GBM bearing mice. SA 3. Evaluate the efficacy of Pt(IV)-BTP-7 drug in orthotopic GBM mouse models. Our research findings could lead to the development of a highly efficacious therapeutic to benefit GBM patients.
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