Modification of biological materials will enable more effective cancer treatment

Modifying the physical characteristics of microscopic biomaterials so that they interact smoothly with body tissues could open up safer and more effective cancer treatments, according to researchers at the Fralin Institute for Biomedical Research at Virginia Tech.

In an online review published in an edition of the Journal of Controlled Release, the research team, led by DaeYong Lee, assistant professor at the Roanoke Cancer Research Center, described how minor changes to therapeutic nanoparticles and biomaterials could improve patient outcomes.

It has recently been recognized that physical characteristics of biomaterials – such as size, structure, shape, charge, mechanical strength, hydrophobicity, and multivalency – regulate the immunological functions of innate immune cells. To achieve the desired innate immune responses in immuno-oncology, biomaterials with different physical properties are created.

«Modifying the physical characteristics of biomaterials is proving to be a powerful tool for controlling immune cell behavior. This approach allows the precise targeting and activation of innate immune cells, such as macrophages and natural killer cells, which play a critical role in the fight against cancer».

Dae-Yong Lee, a member of the Department of Biomedical Engineering and Mechanical Engineering in Virginia Tech’s College of Engineering

Because of his expertise and contributions at the intersection of biomaterials science and cancer immunotherapy, Lee was invited to collaborate with the oncology team.

Although early studies of biomaterials-based approaches showed promising results, many attempts failed in clinical trials, especially for certain tumor types. To overcome these challenges, Lee’s team shifted its focus from optimizing solely chemical properties to fine-tuning the physical characteristics of biomaterials to improve their interaction with immune cells.

This work is based on a study published in Nature Biomedical Engineering in 2024, in which Lee and colleagues engineered positively charged proteins to activate immune pathways.

The synthetic polypeptides promoted the release of mitochondrial DNA, which in turn activated cancer-fighting T cells. In mouse models of advanced breast cancer, these synthesized polypeptides induced a potent antitumor immune response, offering a potentially novel approach to cancer therapy.

The development and optimization of physical properties of biomaterials is an understudied area with great potential.

Notably, translating innovation from the lab to the clinical setting requires addressing issues of scalability, manufacturing, and safety for different patient populations. According to Lee, collaboration between different disciplines, including materials science, immunology and clinical research, is needed to overcome these barriers and lay the groundwork for next-generation cancer therapies.

By focusing on the physical design of biomaterials, Lee’s lab is working to transform cancer therapy for patients who currently face limited treatment options.