Researchers have found a way to enhance radiation therapy using novel iodine
nanoparticles.
Cancer cell death is triggered within three days when X-rays are shone onto
tumor tissue containing iodine-carrying nanoparticles. The iodine releases
electrons that break the tumor’s DNA, leading to cell death. The findings,
by scientists at Kyoto University’s Institute for Integrated Cell-Material
Sciences (iCeMS) and colleagues in Japan and the US, were published in the
journal Scientific Reports.
“Exposing a metal to light leads to the release of electrons, a phenomenon
called the photoelectric effect. An explanation of this phenomenon by Albert
Einstein in 1905 heralded the birth of quantum physics,” says iCeMS
molecular biologist Fuyuhiko Tamanoi, who led the study. “Our research
provides evidence that suggests it is possible to reproduce this effect
inside cancer cells.”
A long-standing problem with cancer radiation therapy is that it is not
effective at the center of tumors where oxygen levels are low due to the
lack of blood vessels penetrating deeply into the tissue. X-ray irradiation
needs oxygen to generate DNA-damaging reactive oxygen when the rays hit
molecules inside the cell.
Tamanoi, together with Kotaro Matsumoto and colleagues have been trying to
overcome this issue by finding more direct ways to damage cancer DNA. In
earlier work, they showed that gadolinium-loaded nanoparticles could kill
cancer cells when irradiated with 50.25 kiloelectron volts of
synchrotron-generated X-rays.
In the current study, they designed porous, iodine-carrying organosilica
nanoparticles. Iodine is cheaper than gadolinium and releases electrons at
lower energy levels.
The researchers dispersed their nanoparticles through tumor spheroids, 3D
tissue containing multiple cancer cells. Irradiating the spheroids for 30
minutes with 33.2 keV of X-rays led to their complete destruction within
three days. By systematically changing energy levels, they were able to
demonstrate that the optimum effect of tumor destruction occurs with 33.2
keV X-ray.
Further analyses showed that the nanoparticles were taken up by the tumor
cells, localizing just outside their nuclei. Shining just the right amount
of X-ray energy onto the tissue prompted iodine to release electrons, which
then caused double-strand breaks in the nuclear DNA, triggering cell death.
“Our study represents an important example of employing a quantum physics
phenomenon inside a cancer cell,” says Matsumoto. “It appears that a cloud
of low-energy electrons is generated close to DNA, causing double strand
breaks that are difficult to repair, eventually leading to programmed cell
death.”
The team next wants to understand how electrons are released from iodine
atoms when they are exposed to X-rays. They are also working on placing
iodine on DNA rather than near it to increase efficacy, and to test the
nanoparticles on mouse models of cancer.
Reference:
Iodine containing porous organosilica nanoparticles trigger tumor spheroids
destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge
energy X-ray ~ by Yuya Higashi, Kotaro Matsumoto, Hiroyuki Saitoh, Ayumi
Shiro, Yue Ma, Mathilde Laird, Shanmugavel Chinnathambi, Albane Birault, Tan
Le Hoang Doan, Ryo Yasuda, Toshiki Tajima, Tetsuya Kawachi and Fuyuhiko
Tamanoi, 14 July 2021, Scientific Reports.