A gold-plated nanoparticle greatly enhanced combination therapy in mouse models of prostate cancer, according to a Northwestern Medicine study published in ACS Nano.
The snowflake-shaped particles amplify radiation and contain immune checkpoint blockades that are released during radiation treatment, triggering an immune response that helps fight cancer. Enhancing radiotherapy and immunotherapy in this small package could improve treatment for a variety of cancers, according to Dong-Hyun Kim, PhD, associate professor of Radiology in the Division of Basic and Translational Radiology Research.
“This could really have a big impact,” said Kim, who is also director of Biomaterials for Image Guided Medicine (BIGMed) laboratory and a member of the Robert H. Lurie comprehensive Cancer Center of Northwestern University.
Radiation therapy is a common treatment strategy for unresectable tumors, often found in prostate or pancreatic cancer. Immunotherapy is another option, quieting immune regulators that normally keep the body’s T-cells cells in check to unleash the immune system on cancer. However, many patients still experience disease progression and death, highlighting a need for more effective therapies.
Curiously, after radiation is applied to a primary tumor site, secondary tumors located further away sometimes exhibit shrinkage, a phenomenon that has been attributed to the radiation triggering an immune response in the body. This is a clear opportunity for immunotherapy, according to Kim, and it inspired his team to create a nano-scale particle to take advantage.
The snowflake-shaped particle holds immune checkpoint blockade antibodies between its spokes and deforms when irradiated, releasing the antibodies that help T-cells and other immune fighters attack cancer. In addition, the gold plating on the nanoparticle helps boost the efficiency of the radiation therapy: Like a rock in the hot sun, the nanoparticle absorbs energy and releases it nearby.
This allows a localized and targeted approach, according to Kim.
“It enhances the effect of the radiation, so we can lower the dose to the patient but the therapeutic effects are preserved,” Kim said.
In the current study, the scientists tested the effectiveness of the nanoparticle in mouse models of prostate cancer. They injected nanoparticles and applied radiation therapy, finding it greatly enhanced tumor cell death when compared to traditional combination therapy.
The subjects also exhibited an increase in cancer-fighting immune cells recruited to the tumor sites, indicating that the immune antibodies were working.
“It was really well-suited for these types of tumors,” Kim said.
The next step, according to Kim, is testing these nanoparticles in human patients. Gold-plated particles could be used for drug delivery and gold particles have been established as safe in humans, so the snowflakes could be ready for human subjects.
“If we can find good candidates, we can try this right away,” Kim said. “It’s ready for translation.”
This work was mainly supported by grants R01CA218659 and R01EB026207 from the National Cancer Institute and National Institute of Biomedical Imaging and Bioengineering. This work was also supported by the Center for Translational Imaging and the Mouse Histology and Phenotyping Laboratory at Northwestern University.
Distinguished Investigator Award
The Academy for Radiology & Biomedical Imaging Research selected Kim to receive the Academy’s 2020 Distinguished Investigator Award. This prestigious honor recognizes individuals for their outstanding contributions to the field of medical imaging.
“This is a big honor, and a big credit to our institution,” Kim said.
Kim’s work focuses on using innovative drug delivery systems to treat cancer, often activating these carriers with external stimuli — both with magnetic field in a previous study, or with radiation therapy in the current study.
“There is a lack of research about synergistic combining radiotherapy with nanoparticles-immunotherapy, so we are trying to develop more translational carriers and clinically relevant models,” Kim said.