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

• Published in: Scientific reports Vol. 9; no. 1; pp. 13275 - 10
• Main Authors: Matsumoto, Kotaro, Saitoh, Hiroyuki, Doan, Tan Le Hoang, Shiro, Ayumi, Nakai, Keigo, Komatsu, Aoi, Tsujimoto, Masahiko, Yasuda, Ryo, Kawachi, Tetsuya, Tajima, Toshiki, Tamanoi, Fuyuhiko
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30-09-2019; Nature Publishing Group
• Subjects: 13; 631/67/1059/485; 639/925/352/2733; Cell Line, Tumor; Female; Gadolinium; Gadolinium - chemistry; Gadolinium - pharmacology; Humanities and Social Sciences; Humans; Metal Nanoparticles - chemistry; Metal Nanoparticles - therapeutic use; multidisciplinary; Nanoparticles; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Ovarian Neoplasms - radiotherapy; Radiation therapy; Science; Science (multidisciplinary); Silica; Spheroids; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; Tumors; X-Ray Therapy; X-rays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-49978-1

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.