Modifying the physical characteristics of microscopic biomaterials to interact seamlessly with the body's tissues could unlock safer and more effective cancer treatments, according to Virginia Tech researchers at the Fralin Biomedical Research Institute at VTC .
In an online review slated for the Feb. 10 issue of the Journal of Controlled Release , a research team led by DaeYong Lee, an assistant professor with the institute's Cancer Research Center in Roanoke, highlighted how slight changes in therapeutic nanoparticles and biomaterials may one day improve treatment outcomes for patients.
The review article describes an underexplored area of cancer therapy: the role of physical properties, such as size, shape, and stiffness, in tuning the body's immune responses.
"Modifying the physical characteristics of biomaterials is proving to be a powerful tool in controlling immune cell behavior," said Lee, who is also a member of the Department of Biomedical Engineering and Mechanics of the Virginia Tech College of Engineering. "This approach allows us to precisely target and activate innate immune cells, such as macrophages and natural killer cells, which play a critical role in the fight against cancer."
Lee's expertise and contributions through high impact publications at the intersection of biomaterials science and cancer immunotherapy earned him an invitation to collaborate with his lab team and review the field in the Journal of Controlled Release article.
While early studies of biomaterial approaches have shown promise, many attempts failed in clinical trials, particularly for certain tumor types. To overcome these challenges, Lee's team is shifting focus from solely optimizing chemical properties to fine-tuning the physical attributes of biomaterials to enhance their interactions with immune cells.
This work builds on a study published in Nature Biomedical Engineering in 2024, in which Lee and his colleagues engineered positively charged proteins to activate immune pathways.
The synthetic polypeptides worked by promoting the release of mitochondrial DNA, which in turn primed cancer-fighting T cells. In mouse models of advanced breast cancer, these engineered [LD1] polypeptides triggered robust antitumor immune responses, offering a potential new approach to cancer therapy.
"The design and optimization of biomaterials' physical properties is an underexplored area with significant potential," said EunHye Kim, first author of the study and a postdoctoral associate in the Lee lab at the Fralin Biomedical Research Institute. "It is exciting to be at the forefront of this rapidly advancing field, driving discoveries that one day may help cancer patients."
Despite these advances, Lee said that challenges remain. Translating innovations from the lab to clinical settings requires addressing scalability, manufacturing, and ensuring safety across diverse patient populations. Collaboration across disciplines — including materials science, immunology, and clinical research — will be essential to overcome these barriers and lay the groundwork for next-generation cancer treatments, Lee said.
Research assistant Katelyn Wahl and biomedical engineering graduate student Erica Guelfi also contributed to the study.
By focusing on the physical engineering of biomaterials, Lee's lab is working to transform cancer therapy for patients who currently face limited treatment options.
"We are very fortunate to have recruited Dr. Lee to Virginia Tech from the MD Anderson Cancer Center in Houston as his work represents one of the essential approaches to next generation cancer therapeutics that we are emphasizing at our cancer research centers in Roanoke and in Washington, D.C.," said Michael Friedlander, executive director of the research institute and Virginia Tech's vice president for health science and technology. "His recruitment was made possible with the help of a transformational gift from the Red Gates Foundation that is helping Virginia Tech's growth in cancer research."
[LD1]Polypeptides
