Human white blood cells with internalized particles (blue is cell nucleus, red is membrane, and green is RNA nanoparticles). Submitted by Marina Dobrovolskaia.

FREDERICK, Md. -- The Frederick National Laboratory for Cancer Research is opening potential new avenues for coaxing the human immune system to fight cancer and other diseases through microscopic particles, or nanoparticles.

The use of nanoparticles to transport drugs to cancer cells is a growing field that has piqued scientists’ interest over the last two decades. Nanoparticles show potential because they can directly target and treat cancer cells. 

One class of nanoparticles, nucleic acid nanoparticles, has emerged as a group of potential therapeutics to treat cancer and other diseases. These particles are favorable because they can be programmed in different shapes and sizes to trigger different immune responses. But specific mechanisms for manipulating nucleic acid nanoparticles to achieve these various immune responses are not fully understood. There have been no clinical trials involving these nanoparticles to date. 

Scientists at the Frederick National Laboratory in collaboration with University of North Carolina at Charlotte and Ball State University are addressing this gap in the research and have come up with a molecular language to help characterize the properties of these nanoparticles, which could help accelerate their clinical translation. 

“With these particles, there are so many things that you can optimize,” said Marina Dobrovolskaia, Ph.D., MBA, head of the Nanotechnology Characterization Laboratory’s Immunology Section at the Frederick National Laboratory. “The more things that you can modify, the more opportunities you have to make something do only what you want it to do, such as stimulating immune response to improve cancer therapy.”    

Dobrovolskaia was one of the lead authors on a recent study published in Nano Letters that established a library of 25 nucleic acid nanoparticles and their properties that could help scientists better understand their immunological effects. 

The research team used human blood for the study collected through the Research Donor Program, managed by the Frederick National Laboratory’s Occupational Health Services, to help characterize the nanoparticles’ interaction with blood cells and their immune recognition. 

They determined that unlike traditional therapeutic nucleic acids, these nanoparticles can be delivered directly to cells to trigger a response, thus potentially minimizing harmful side effects. The scientists also found that the nucleic acid nanoparticles induce certain types of interferons, or proteins normally released by cells in response to viruses. The number of interferons produced in response to the nanoparticles can be fine-tuned to minimize toxic side effects based on the nanoparticle’s structure, shape, and connectivity, among several other key findings. 

“My goal is to enable the field to design new therapeutics by providing the methods, screening tools, and other ideas of what to look for if you want to translate them into the clinic,” said Dobrovolskaia. “This is the mission of the Nanotechnology Characterization Laboratory to provide education and knowledge sharing.” 

While the research is still in early stages, Dobrovolskaia and her collaborators are hopeful that their characterization of nucleic acid nanoparticles could make a contribution to the understanding of immunotherapy, when the body’s own immune system is harnessed to fight cancer and other diseases. They are also hopeful that their research will help bridge the gap between basic research and clinical translation of nucleic acid nanoparticles to treat cancer and other diseases. The research team has also filed for a patent describing their findings. 

“In the current field everyone is looking at how we can use the body’s own immune defense to improve therapy outcomes in patients with cancer and AIDS, and this fits with the Frederick National Laboratory’s mission, with these materials, it looks like there are a lot of opportunities,” said Dobrovolskaia.

By Max Cole, staff writer

Image: Human white blood cells with internalized particles (blue is cell nucleus, red is membrane, and green is RNA nanoparticles). Submitted by Marina Dobrovolskaia. 

This research collaboration is funded by the NIH (NCI contract HHSN261200800001E to Leidos Biomedical Research and NIH grant R01GM120487 to Dr. Kirill Afonin at the University of North Carolina at Charlotte.