Radiation has been a mainstay cancer therapy for almost 100 years. But its potent cell-killing power, so effective against tumors, is a double-edged sword when healthy tissue gets in the way.
Borrowing from one of nature’s toughest survivors, researchers at University of Iowa Health Care, MIT, and Brigham and Women’s Hospital, are creating a unique approach to protect healthy tissue during radiation therapy.
The protection comes from tardigrades, microscopic creatures with an extraordinary ability to withstand extreme conditions, including radiation levels 2,000 to 3,000 times higher than humans can tolerate.
This radioprotective effect is due in part to a damage suppressor (Dsup) protein that is unique to tardigrades. The Dsup protein binds to and protects DNA from strand breaks caused by radiation.
In the new study, the researchers created polymer-lipid based nanoparticles that deliver the mRNA instructions to make the tardigrade Dsup protein. The nanoparticles were able to target the type of cells that line oral and rectal cavities, which are most commonly damaged in patients receiving radiation therapy for head and neck cancers and prostate cancer.
When the nanoparticles were studied in mice models of cancer, they produced sufficient Dsup protein to protect normal cells from the damaging effect of radiation therapy, while still allowing effective treatment of the tumor.
“Radiation is an important tool for treating all kinds of cancer, but the side effects caused by radiation-induced damage to healthy tissue can be severe enough to stop patients from completing the therapy,” says James Byrne, MD, PhD, assistant professor of radiation oncology at UI Health Care and a member of Holden Comprehensive Cancer Center. “This is an entirely novel approach for protecting healthy tissue and may eventually offer a way to optimize radiation therapy for patients while minimizing these debilitating side effects.”
Recent findings about a new tardigrade species, which revealed additional radioprotective proteins, may make this approach even more feasible.
Byrne and Giovanni Traverso, an associate professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital, are the senior authors of the study, published on Feb. 26 in Nature Biomedical Engineering. The paper’s lead authors are Jianling Bi, a research scientist at the UI, and Ameya Kirtane, an assistant professor of pharmaceutics at the University of Minnesota.
Other authors of the paper include Netra Rajesh, Chaoyang Tang, Miguel Jimenez, Emily Witt, Megan McGovern, Arielle Cafi, Samual Hatfield, Lauren Rosenstock, Sarah Becker, Nicole Machado, Veena Venkatachalam, Dylan Freitas, Xisha Huang, Alvin Chan, Aaron Lopes, Hyunjoon Kim, Nayoon Kim, Joy Collins, Michelle Howard, Srija Manchkanti, and Theodore Hong.
The research was funded by the Prostate Cancer Foundation Young Investigator Award, the Department of Defense Prostate Cancer Program Early Investigator Award, a Hope Funds for Cancer Research Fellowship, the American Cancer Society, the National Cancer Institute, MIT’s Department of Mechanical Engineering, and the Advanced Research Projects Agency for Health.
Byrne received the prestigious NIH Director’s New Innovator Award to support his work developing unique, biocompatible materials to reduce the side effects of radiation therapy with the goal of improving outcomes and quality of life for cancer patients.