Nontoxic Molecule Able to Store Radiation Securely

Microscopic “bubbles” have been found to be safe and effective storage lockers for harmful isotopes that emit ionizing radiation for treating tumors.

The findings can benefit patient health and advance radiation therapy used to treat cancer and other diseases, according to John M. Tomich, a professor of biochemistry and molecular biophysics who is affiliated with the Kansas State University’s (Manhattan, USA) Johnson Cancer Research Center.

Prof. Tomich conducted the study with Dr. Ekaterina Dadachova, a radiochemistry specialist at Albert Einstein College of Medicine (New York, NY, USA), along with researchers from Japan and Germany. They recently published their findings in the study ahead of print February 22, 2014, in the journal Biochimica et Biophysica Acta.

The study looks at the ability of nontoxic molecules to store and deliver potentially harmful alpha emitting radioisotopes—one of the most effective forms of radiation therapy.

In 2012, Prof. Tomich and his research lab team combined two related sequences of amino acids to form a very small, hollow nanocapsule similar to a bubble. “We found that the two sequences come together to form a thin membrane that assembled into little spheres, which we call capsules,” Prof. Tomich said. “While other vesicles have been created from lipids, most are much less stable and break down. Ours are like stones, though. They're incredibly stable and are not destroyed by cells in the body.”

The ability of the capsules to stay intact with the isotope inside and remain undetected by the body’s clearance systems prompted Prof. Tomich to investigate using the capsules as unbreakable storage containers that can be used for biomedical research, particularly in radiation therapies. “The problem with current alpha-particle radiation therapies used to treat cancer is that they lead to the release of nontargeted radioactive daughter ions into the body,” Dr. Tomich said. “Radioactive atoms break down to form new atoms, called daughter ions, with the release of some form of energy or energetic particles. Alpha emitters give off an energetic particle that comes off at nearly the speed of light.”

These particles are like a car sliding on ice, according to Prof. Tomich. They are very powerful but can only travel a short distance. The alpha particle destroys DNA when they collide and whatever critical cellular pieces are in its way. Similarly, the daughter ions recoil with high energy on ejection of the alpha particle—similar to how a gun recoils as it is fired. The daughter ions have enough energy to escape the targeting and containment molecules that currently are in use.

“Once freed, the daughter isotopes can end up in places you don’t want them, like bone marrow, which can then lead to leukemia and new challenges,” Dr. Tomich said. “We don’t want any stray isotopes because they can harm the body. The trick is to get the radioactive isotopes into and contained in just diseases cells where they can work their magic.”

The radioactive compound that the scientists work with is ²²⁵Ac (Actinium), which on decay releases four alpha particles and numerous daughter ions. Drs. Tomich and Dadachova tested the retention and biodistribution of alpha-emitting particles trapped inside the peptide capsules in cells. The capsules readily enter cells; once inside, they migrate to a position next to the nucleus, where the DNA resides.

Drs. Tomich and Dadachova found that as the alpha particle-emitting isotopes decayed, the recoiled daughter ion collides with the capsule walls and essentially bounces off them and remains trapped inside the capsule. This completely blocked the release of the daughter ions, which prevented uptake in certain nontarget tissues and protected the subject from harmful radiation that would have otherwise have been releases into the body.

Dr. Tomich stressed that more studies are needed to add target molecules to the surface of the capsules. He foresees that this new approach will provide a safer option for treating tumors with radiation therapy by reducing the amount of radioisotope required for destroying the cancer cells and reducing the side effects caused by off-target accumulation of the radioisotopes. “These capsules are easy to make and easy to work with,” Dr. Tomich said. “I think we’re just scratching the surface of what we can do with them to improve human health and nanomaterials.”

Related Links:
Kansas State University
Albert Einstein College of Medicine