Nanoparticles carrying iodine atoms can break cancer DNA and target the centre of tumour tissues with the help of X-rays, paving the way for more effective radiotherapy.
In 2018, the International Agency for Research on Cancer reported 18.1 million new cases and 9.5 million cancer deaths worldwide. By 2040, the number of new cancer cases is expected to jump to 29.5 million and deaths associated with cancer will rise to 16.4 million. Given the increasing prevalence of cancer, researchers have been pouring their resources to develop more effective treatments and drugs to treat, minimise, and prevent the re-emergence of these rogue cells.
One of the most well-known and widely used cancer treatments is radiotherapy, which involves using high-energy beams or particles, particularly that of X-rays, to kill cancer cells and tumours. However, a long-standing problem that has hindered advancements in radiation therapy is that this method is ineffective to target the centre of tumour tissues. This is because blood vessels cannot penetrate as deeply into the tissues, causing lower oxygen levels in those areas. As X-ray irradiation requires oxygen to generate the free radicals needed to destroy the DNA of tumours, the centre of tumour tissues largely remain unscathed
With a mission to solve this problem, scientists at Kyoto University’s Institute for Integrated Cell-Material Sciences have joined hands with colleagues in Japan and the US to innovate a new radiotherapy approach. After a series of experiments, the team found that by injecting iodine-carrying nanoparticles into tumour tissues and irradiating the tumour with X-rays, iodine atoms can be induced to release electrons that break the tumour’s DNA, thereby leading to cell death.
“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,” said molecular biologist Fuyuhiko Tamanoi, who led the study. “Our research provides evidence that suggests it is possible to reproduce this effect inside cancer cells.”
Previously, Tamanoi, together with Kotaro Matsumoto and colleagues have attempted to overcome this issue by exploring more direct ways to disrupt cancer DNA, such as using gadolinium-loaded nanoparticles, which can kill cancer cells when irradiated with 50.25 kiloelectron volts of synchrotron-generated X-rays.
In the current study, the scientists took on a different approach by designing porous, iodine-carrying organosilica nanoparticles. Compared to gadolinium, iodine is not only cheaper but can also release electrons at lower energy levels, thus suggesting that less powerful beams of X-rays would be sufficient to generate the much-needed free radicals.
To test this hypothesis, the scientists dispersed the nanoparticles through tumour spheroids, which are 3D tissues containing multiple cancer cells, and irradiated the tissues with X-rays. Their experiment showed that irradiating the spheroids for 30 minutes with 33.2 keV of X-rays led to the complete destruction of the cancer cells within three days. Furthermore, after systematically changing the energy levels of the X-rays, the team was able to establish that the optimum effect of tumour destruction occurs with 33.2 keV X-ray.
The team was also interested in finding out how exactly these nanoparticles function as mini “bombs” against tumours. Based on their analyses, it was discovered that the nanoparticles were taken up by the tumour cells and localised just outside their nuclei. Upon shining the right amount of X-ray energy onto the tissue, the iodine inside the nanoparticles started releasing electrons, which caused double-strand breaks in the nuclear DNA, thus triggering cell death.
“Our study represents an important example of employing a quantum physics phenomenon inside a cancer cell,” explained 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.”
With these optimistic findings, the team is excited to learn more about how the electrons are released from iodine atoms when they are exposed to X-rays. Currently, they are working on placing iodine on DNA rather than near it to increase the efficacy of their novel approach, and are also looking into extending the research to cancer mouse models.
Source: Higashi et al. (2021). Iodine containing porous organosilica nanoparticles trigger tumor spheroids destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge energy X-ray. Scientific Reports, 11, 14192.