It is hard to deny the power of heavy metal – not so much Metallica but X-ray-enhancing nanoparticles made of hafnium.

In a proof-of-principle study reported at the American Society of Clinical Oncology meeting in Chicago, patients with inoperable, advanced soft tissue sarcoma were able to successfully undergo surgical resection after neoadjuvant radiotherapy with the novel heavy metal nanoparticle, NBTXR3. The latter, a nanoparticle consisting of hafnium oxide crystals, has been developed by Nanobiotix, a spin-off of the State University of New York at Buffalo and now based in Paris, France.

Bernd Muehlenweg, head of business development at Nanobiotix, noted that in soft tissue sarcoma, about 60% of patients have unresectable tumours and their standard-of-care for these patients is to receive radiotherapy to debulk the tumour mass prior to surgery. If the radiotherapy is optimal, then the surgeon can remove the mass with clean margins. However, if the tumour is not sufficiently debulked, the surgeon has to take it out in pieces, and this greatly increases the patient’s risk for developing metastases from residual tumour cells.

In a Phase I study of NBTXR3, 17 patients with advanced soft tissue sarcoma had their tumours treated with nanoparticles prior to external beam radiation therapy. After five weeks of radiotherapy, all patients underwent successful resection with wide surgical margins.

The particle has a negatively charged coating, explained Mr Muehlenweg, and the charge facilitates particle uptake by tumour cells. Once inside, due to the inherent properties of the heavy metal, the intensity of the radiation is amplified nine-fold. Side effects were minimal and were related to discomfort associated with the particle’s administration, which is via intratumoural injection.

Mr Muehlenweg emphasised that NBTXR3 is not a radio-sensitiser, saying that “there is no systemic delivery here because this is not a biological treatment. What we’re inducing is a purely physical effect". The particle intensifies the effects of radiation through localised amplification, and this, as opposed to radio-sensitisers, spares the surrounding healthy tissue during radiotherapy.

Furthermore, hafnium is inert in the human body, and therefor eis not viewed, in the regulatory sense, as a drug. The European designation for NBTXR3 is as a medical device.

Commenting on the study results, Emiliano Calvo, a panel member on ASCO’s scientific committee for developmental therapeutics, acknowledged the potential of this approach. “It seems to have a real synergistic effect with the radiation therapy administered to patients with unresectable and, usually, highly resistant, sarcomas, including some very impressive tumour remissions in these patients. And this is not at the expenses of higher toxicity, since its tolerance profile seems to be quite favorable as well.”

Development of NBTXR33 is ongoing and it will be tested next in head and neck cancer.