Although 60% of cancer patients receive a radiotherapy treatment, many cannot withstand the doses required to destroy the tumour because they do not respond sufficiently or not at all to treatments and sometimes even develop resistance to these treatments. “To make radiotherapy even more effective, we must succeed in selectively increasing the dose of x-rays inside the tumour without touching the surrounding healthy tissues and thus saving them from destruction. This is the purpose of the nanotechnology that we are developing,” explains Laurent Lévy, cofounder and CEO of nanomedicine company Nanobiotix.The Paris-based company has designed inert nanoparticles capable of strongly absorbing x-rays and locally generating a substantial energy store right at the heart of the malignant cell. These particles, which are activated by an external field (x-ray, MRI and laser), have been the subject of six industrial property patent families.The NanoXray technology is based on crystallised and inorganic hafnium-oxide nanoparticles, 50 nm in diameter, that fall under Class III medical devices under European regulation. After they are injected into the tumour, these nanoparticles build up in the cancer cells where they are activated by the x-rays. Thanks to the physical properties of hafnium oxide, these particles will generate very large quantities of electrons only when exposed to ionising radiation. This amplifies the lethal dose of energy in the tumour by as much as ninefold.The company is developing three products to meet the specific clinical needs for different cancers. “All our products have an identical core in hafnium oxide but are all different because of the composition of the nanoparticle coating and how they are used," Levy says. For example, the first generation of nanoparticles, NBTXR3, was designed to be injected directly into the malignant tumour in indications for primary liver cancer, glioblastoma (a specific form of brain cancer), rectal cancer, prostate cancer or head and neck cancers. The second generation of nanoparticles, NBTX-IV, is injected intravenously to enable the product to reach the tumour as well as the surrounding tissues, which may be already invaded locally by cancer cells. Lastly, the third generation of nanoparticles, NBTX-TOPO, has been designed as a gel for surgical use, applied in order to prepare the tumour bed for postoperative chamber radiotherapy for breast cancers, brain tumours and retroperitoneal soft tissue sarcomas.The final results of the phase 1 clinical study of BTXR3 nanoparticles on some 20 patients suffering from advanced soft tissue sarcoma were presented at the 50th annual conference of the American Society for Clinical Oncology (ASCO) held in Chicago a few months ago. They demonstrate the feasibility of injecting Nanobiotix nanoparticles into the tumour mass for different types and volumes (55.06 ml to 3682.56 ml) of tumours. "This study confirms that our nanoparticles do not enter the surrounding healthy tissue. It also provides evidence of excellent tolerance, excellent local safety as well as promising signs of antitumour efficacy,” Lévy says. These positive results will enable Nanobiotix to start preparing for the last pivotal clinical phase that should enable us to register the product and obtain EC marking in 2016.Nanobiotix has partnered with a Taiwanese biopharmaceutical company to conduct this pivotal trial and to speed up its expansion in Asia Pacific. Nanobiotix also recently opened a subsidiary in the Massachusetts Life Science Center in the United States.