Lee’s lab discovers nano carrier to fight GBM
A recent study from researchers at McGovern Medical School discovered a novel engineered exosome model to help deliver therapeutic treatments to glioblastoma tumors which could potentially enhance treatments for a notoriously fatal cancer.
Findings from the study, led by Tae Jin Lee, PhD, assistant professor in the Vivian L. Smith Department of Neurosurgery, was published in Nano Letters.
“There are not many therapeutic options for patients with glioblastoma, which is one of the most aggressive forms of brain cancer,” Lee said. “So, we wanted to focus on nanotechnology to develop a new treatment by taking advantage of exosomes, which are small and naturally produced “cargo messengers,” that can be engineered to carry therapeutics and target GBM cancer cells.”
The lab’s research found that lightly treating exosomes with the enzyme trypsin allows the exosomes to be used as a targeted drug carrier. Combining these with cancer-targeting ligands on the exosomes’ surface, the modified nano carriers can seek out cancer cells and deliver therapeutics.
“In this study, we used tumor-suppressing microRNA (miRNA), small, non-coding pieces of RNA that can regulate multiple cancer-related genes simultaneously,” Lee said. “Our engineered exosome model can be translated as a new therapeutic that can be used in conjunction with the standard of care.”
In previous research, the lab discovered that miRNA-138 could be a potential tumor-suppressive miRNA, and that it could be a sensitizer of GBM cancer cells to chemotherapy. However, miRNA is not delivered to the body easily and can cause the degradation in the blood stream.
“This prompted us to explore safe, cost-efficient, and targeted ways to deliver miRNAs into the GBM tumor cells,” Lee said. “We modified exosome surfaces using a light enzyme digestion and labeled their surface with cancer cell-targeting ligands like folates with significantly increased efficiency, then filled their inside with miRNA-138.”
With this improved carrier platform, the group was able to deliver tumor-suppressive miRNA-138 into both GBM tumor cells and surrounding tumor-associated macrophages, which both support each other to sustain tumor growth.
“After the treatment, we observed that modulating tumor-supporting innate immunity by targeting TAMs with miRNA-138 added another layer of anti-tumor immunity in murine models, suggesting a bright side for combination with conventional T-cell-based immunotherapies,” Lee said. “These findings show that exosomes are a viable method for targeted drug delivery, as opposed to traditional yet immunogenic lipid-based nanoparticles.”
Additionally, Lee said that miRNA showed therapeutic benefits in terms of drug resistance that is a common issue for patients with GBM. Moving forward, the lab hopes their research will lead to additional studies and potential uses for other types of cancer.
“With these new results, we are interested in developing more robust combination therapy with immunotherapy, and chemo or radiotherapy that requires a reprogrammed tumor microenvironment to be effective,” Lee said. “We also aim to improve our model by testing new cancer-specific ligands to increase cancer-specific targeting and target other tumor-supporting immune cells, like regulatory T cells, within the tumor microenvironment.”
The study is led by corresponding authors Lee and Ji Young Yoo, PhD, associate professor in the Department of Neurosurgery. The first author is Grace H. Nguyen. Authors from UTHealth Houston include Hongyu Wang, MD, PhD, Cynthia Ju, PhD, Holger K. Eltzschig, MD, PhD, and Zhongming Zhao, PhD. Additional contributors for the study are MinHye Noh, PhD, Jin Muk Kang, PhD, Alexandra A. Miller, Jiyeon Kim, and Minxin Huang.