Feb 24 2021
Glioblastoma multiforme, the most common and aggressive form of primary brain tumor, has a survival rate of just five years. It is particularly challenging to treat, with existing therapies depending on chemotherapy, radiation, surgery, and their combinations.
Sheereen Majd, assistant professor of biomedical engineering, is the first to report on targeted delivery of Dp44mT to malignant tumors. Image Credit: University of Houston.
Two of the major challenges in the treatment of gliomas include poor transport of chemotherapeutics across the blood brain barrier and undesired side effects of these therapeutics on healthy tissues. To get enough medicine across the blood brain barrier, a high dosage of medication is required, but that introduces more toxicity into the body and can cause more problems.
Sheereen Majd, Assistant Professor of Biomedical Engineering, University of Houston
In a study published in and featuring on the cover of the January issue of Advanced Healthcare Materials, Majd describes a new glioma-targeted nano-therapeutic that will just tackle tumor cells, providing lower side effects and higher effectiveness.
An iron chelator called Dp44mT (Di-2-pyridylketone-4, 4-dimethyl-3-thiosemicarbazone) is an effective medication that is well-known to suppress tumor progression but had not been used to treat brain tumors before this study. The chelator starves cancer cells by removing excess iron.
Majd used clues from the tumors themselves to develop a Dp44mT-loaded nano-carrier to which glioma tumors would be attracted since the tumors present several IL13 (Interleukin) receptors. Since the IL13 receptors are plentiful, Majd added IL13 ligands to her FDA-approved biodegradable polymer carrier (incorporating the Dp44mT) so the receptors would attract the ligands, receiving the medicine.
Before using this new carrier, the Dp44mT drug would be administered but could reach any place within the body, even those where it is not meant to go.
It’s like an envelope with no address on it. It can land anywhere, and with toxins inside it could kill anything. Now, with our targeted delivery, we put an address on the package and it goes directly to the cancer cells.
Sheereen Majd, Assistant Professor of Biomedical Engineering, University of Houston
Moreover, aggressive brain tumors tend to develop higher multidrug resistance, which makes them almost impenetrable for common chemotherapeutics such as doxorubicin or temozolomide.
There is, hence, an urgent need for more effective therapeutic formulations with the ability to overcome drug resistance in aggressive glioma tumors and to kill these malignant cells without damaging the healthy tissues.
Sheereen Majd, Assistant Professor of Biomedical Engineering, University of Houston
The research by Majd, which involved testing the nano-therapeutic both in vivo and in vitro, is the first one to report on targeted delivery of Dp44mT to malignant tumors.
Journal Reference:
Kang, Y. J., et al. (2021) Biodegradable Nanoparticles: Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation. Advanced Healthcare Materials. doi.org/10.1002/adhm.202170007.