Nanoparticle Harnesses Powerful Radiation Therapy for Cancer
Researchers at the University of Missouri have demonstrated the ability to create a multi-layered harness nanoparticle that can safely encapsulate powerful alpha-emitting radioisotopes and target tumors. The resulting nanoparticles not only offer the possibility of delivering tumor-killing alpha emitters to tumors, but also sparing healthy tissue from radiation damage. J. David Robinson and his colleagues published their findings in the journal PLoS One.
Typically, when radiation treatment is recommended for cancer patients, doctors are able to deliver radiation from a source outside the body or they might inject one of several radiopharmaceuticals that emit low-energy radiation known as beta particles. For years, scientists have been studying how to use "alpha emitters," which are radioactive elements that release high-energy alpha particles that would more effectively damage cancer cells and trigger cell death. The challenge to using alpha emitters is that the decay elements, the so-called daughters, are themselves highly toxic and difficult to contain in the vicinity of the tumor, thus causing significant damage to healthy tissues.
"If you think of beta particles as slingshots or arrows, alpha particles would be similar to cannon balls," said Dr. Robertson. He explains that recent work has shown that alpha particles can be effective in treating cancer in specific instances. "For example, a current study using radium-223 chloride, which emits alpha particles, has been fast-tracked by the U.S. Food and Drug Administration because it has been shown to be effective in treating bone cancer. However, it only works for bone cancer because the element, radium, is attracted to the bone and stays there. We believe we have found a solution that will allow us to target alpha particles to other cancer sites in the body in an effective manner."
In their studies, Dr. Robertson and colleagues from Oak Ridge National Laboratory and the School of Medicine at the University of Tennessee in Knoxville used the isotope actinium-225, an element that when it decays produces a high-energy alpha particle and radioactive daughter elements, which are also capable of emitting alpha particles. Efforts to contain the daughter elements using traditional molecular constraints proved fruitless because the emitted alpha particles broke the chemical bonds necessary to hold the daughter elements in place.
The Missouri team solved this problem by sequestering actinium-225 in the core of a gold-coated magnetic nanoparticle. The magnetic layer, comprised of gadolinium phosphate, serves to increase retention of the daughter elements while simplifying particle purification and the gold coating provides a surface to which tumor-targeting molecules can be attached. In the experiments described in their current publication, the researchers used an antibody that targets a receptor found on the surface of lung tumors.
"Holding these alpha emitters in place is a technical challenge that researchers have been trying to overcome for 15 years," Dr. Robertson said. "With our nanoparticle design, we are able to keep more than 80 percent of the element inside the nanoparticle 24 hours after it is created." While alpha particles are extremely powerful, they do not travel very far, so when the nanoparticles get close to the targeted cancer cells, the alpha particles are more selective at damaging cancer cells but not surrounding cells.
This work is detailed in a paper titled, "Gold coated lanthanide phosphate nanoparticles for targeted alpha generator radiotherapy." Investigators from the Oak Ridge National Laboratory and the University of Tennessee also participated in this study. A copy of this paper is available at no charge at the journal’s website.