Destruction of tumor mass by gadolinium-loaded nanoparticles irradiated with monochromatic X-rays: Implications for the Auger therapy

Abstract

Synchrotron generated monochromatic X-rays can be precisely tuned to the K-shell energy of high Z materials resulting in the release of the Auger electrons. In this work, we have employed this mechanism to destruct tumor spheroids. We first loaded gadolinium onto the surface of mesoporous silica nanoparticles (MSNs) producing gadolinium-loaded MSN (Gd-MSN). When Gd-MSN was added to the tumor spheroids, we observed efficient uptake and uniform distribution of Gd-MSN. Gd-MSN also can be taken up into cancer cells and localize to a site just outside of the cell nucleus. Exposure of the Gd-MSN containing tumor spheroids to monochromatic X-ray beams resulted in almost complete destruction. Importantly, this effect was observed at an energy level of 50.25 keV, but not with 50.0 keV. These results suggest that it is possible to use precisely tuned monochromatic X-rays to destruct tumor mass loaded with high Z materials, while sparing other cells. Our experiments point to the importance of nanoparticles to facilitate loading of gadolinium to tumor spheroids and to localize at a site close to the nucleus. Because the nanoparticles can target to tumor, our study opens up the possibility of developing a new type of radiation therapy for cancer.

Excretable, ultrasmall hexagonal NaGdF4:Yb50% Nanoparticles for bimodal imaging and radiosensitization

“…A new study has shown near complete destruction of tumor spheroids of human ovarian cancer (OVCAR8) when incubated with gadolinium loaded mesoporous silica nanoparticles (Gd-MSN) prior to exposure to monochromatic 50.25 KeV X-rays. [70] It is worth noting that the Gd-MSNs accumulated in the lysosomes located close to the cell nucleus. This highlights the importance not only of the energy compatibility made possible by using tunable monochromatic beam radiation, but also by the proximity of the radiosensitizers to the nucleus in order to destroy the DNA of the tumor cells.…”

Convergence of the Study on Monochromatic X-rays and the Research on Nanoparticles Opens Up a Possibility to Develop a New Type of Radiation Therapy

“…In our study, SPring-8 synchrotron radiation facility located in Harima, Japan, was used ( Figure 1B). The storage ring is operated with a constant storage ring current of 100 mA [9]. The monochromatic X-rays from a bending magnet were shaped by horizontal and vertical slits.…”

“…The monochromatic X-rays from a bending magnet were shaped by horizontal and vertical slits. The incident beam size is 1.4 mm in height and 1.4 mm in width at the sample position [9].…”

“…Advantageous properties of nanoparticles such as tumor targeting have important implication for radiation therapy. Another approach that has recently emerged is to deliver high Z elements by nanoparticles into tumor mass and to irradiate with a monochromatic X-ray beam [9]. In this study, gadolinium was loaded onto nanoparticles and distributed throughout tumor spheroids.…”

Nanocomposite Polymer Scaffolds Responding under External Stimuli for Drug Delivery and Tissue Engineering Applications

“…X‐ray irradiation is linked to high energy electromagnetic beam inducing ionization radiation. Thus, heavy metal NPs such as gold NPs will enhance the radiation dose through an increased absorption of X‐rays, and this will lead to a subsequent ejection of electrons, known as the Auger cascade . This irradiation is noninvasive, penetrates the full body but the main drawbacks include risks for healthy tissues, complexity of use, a high cost, and a specific implementation.…”