Nanobiotix and NBTXR3: How Hafnium Oxide Nanoparticles Enhance Radiotherapy

By Ankit SinghReviewed by Frances BriggsMay 12 2026

Nanobiotix is developing a cancer treatment designed to make radiotherapy more effective in solid tumors. Its lead product, NBTXR3, uses hafnium oxide nanoparticles that are injected into a tumor before radiation treatment.

Image Credit: Mark_Kostich/Shutterstock.com

The idea is straightforward. Hafnium absorbs X-rays more efficiently than ordinary tissue. When exposed to radiation, the nanoparticles release energy inside tumor cells, increasing local damage without raising the radiation dose delivered to surrounding healthy tissue.

Building a Science from Scratch

Nanobiotix was founded in 2003 as a spin-off from the State University of New York at Buffalo, based on research by Laurent Levy. The company is headquartered in Paris, France, and also has offices in Cambridge, Massachusetts, with affiliates in Spain and Germany.

Between 2007 and 2010, early research focused on what the team called the NanoXray program, a systematic effort to understand how high-atomic-number nanoparticles interact with X-ray beams at the cellular level.

In 2011, the company launched its first Phase I/II clinical study of NBTXR3 in human patients, marking the treatment of the first patient in that trial. Nanobiotix went public in 2012 on Euronext Paris and later listed on the NASDAQ Global Select Market under the ticker NBTX, giving it access to capital on both sides of the Atlantic.^1,2,3

Physics as Medicine

NBTXR3 is based on hafnium, an element with an atomic number of 72. Hafnium atoms absorb X-ray photons more effectively than the carbon, oxygen, and hydrogen atoms that make up most biological tissue.

Before radiotherapy, the nanoparticles are injected directly into a solid tumor. Cancer cells then take them up through endocytosis. The particles remain in place during a treatment course that may last several weeks.⁴

When radiation is delivered, the hafnium absorbs energy and releases it as secondary electrons, including photoelectrons and Auger electrons. These electrons travel only short distances, but enough to generate reactive oxygen species and cause complex double-strand DNA damage inside tumor cells.

Clinical studies cited by the company and in the literature suggest that, once activated by radiotherapy, NBTXR3 can increase the energy deposited in tumor cells by up to nine times compared with radiotherapy alone, without increasing exposure to nearby healthy tissue.^4,5

Because the mechanism is physical rather than molecular, it does not depend on a tumor carrying a specific mutation or expressing a particular surface marker. That means, at least in theory, that it could be used across a wide range of solid tumors.

After each radiation session, the particles return to an inactive state. This allows a single injection to remain active across multiple radiotherapy sessions.^4,5

The Immune Layer

More recent research has looked beyond the local radiation effect and focused on the immune response.

A study published in Cancer Cell International found that NBTXR3, when activated by radiotherapy, increased markers linked to immunogenic cell death. It also reported changes in the immunopeptidome, the set of peptide fragments displayed on cell surfaces, and increases in immune cell infiltrates including CD⁴⁺, CD⁸⁺ and CD⁶⁸⁺ cells.⁶

The same study also found changes in T-cell receptor repertoire diversity, including in distant untreated tumors. That has drawn attention because it suggests the treatment may have effects beyond the site of injection.

A separate report in Therapeutic Advances in Medical Oncology described increased cGAS-STING-mediated type I interferon signaling when NBTXR3 was combined with radiotherapy. That pathway is involved in activating effector T cells and shaping immune memory. In preclinical models, the combination was associated with reduced metastatic spread.

Those findings have led to interest in whether NBTXR3 could trigger a broader anti-tumor immune response, including what is often called the abscopal effect.⁷

They also help explain why the company has been testing the treatment alongside checkpoint inhibitors. The logic is that local radiation damage may make tumors more visible to the immune system, while immunotherapy may help sustain that response.^6,8

Clinical Validation Across Tumor Types

Image Credit: Rabizo Anatolii/Shutterstock.com

The first major regulatory milestone for Nanobiotix arrived in 2019, when NBTXR3, marketed in Europe under the brand name Hensify. It became the first radioenhancer to receive a CE mark, granting it market approval in 27 European Union countries for the preoperative treatment of locally advanced soft tissue sarcoma.

The approval followed a Phase 2/3 trial of 176 patients in which those receiving NBTXR3 plus radiotherapy achieved a significantly higher rate of pathological complete response than patients treated with standard radiotherapy alone.^4,9

Clinical development has since advanced to head and neck squamous cell carcinoma (HNSCC). A Phase 1 dose-expansion study published in JAMA Otolaryngology looked at patients with locally advanced HNSCC who were not eligible for cisplatin or cetuximab. In that study, the objective response rate in the injected primary tumor was 82 %, with a complete response rate of 64 %. Median overall survival was 18.1 months.

Updated Phase 1 results presented at the 2025 ASTRO Annual Meeting reported a 95 % disease control rate in NBTXR3-injected lesions across 91 evaluable patients with recurrent or metastatic HNSCC. In patients who had not previously received anti-PD-1 therapy, the disease control rate was reported at 63 %. 

In primary cutaneous melanoma, reported Phase 1 results showed an objective response rate of 47.4 % and a disease control rate of 78.9% across 19 evaluable patients. Median overall survival was 14.6 months in a heavily pretreated group whose disease had progressed after several earlier lines of therapy, including anti-PD-1 treatment.

Beyond those settings, Nanobiotix says it is evaluating NBTXR3 in 14 clinical trials across other solid tumors, including non-small cell lung cancer, pancreatic cancer, and prostate cancer.^4,12

A Global Partnership Structure

In July 2023, Nanobiotix announced a global licensing, co-development, and commercialization deal with Janssen Pharmaceutica NV, a Johnson & Johnson company. The agreement gave Janssen exclusive worldwide rights to develop and commercialize NBTXR3.

Under that arrangement, the Phase 3 head and neck cancer trial known as NANORAY-312 transferred to Johnson & Johnson in 2024. Interim data are expected in the first half of 2027.^8,13

The deal has given the program access to the resources of a much larger pharmaceutical group. It also shifts part of the development burden away from a smaller biotech company.

Nanobiotix has also worked with the University of Texas MD Anderson Cancer Center since 2019. That collaboration has supported several Phase 1 and Phase 2 studies across tumor types and treatment combinations.¹²

Built for Broad Application

Nanobiotix is making a relatively simple claim: that radiotherapy can be made more effective inside a tumor without increasing the dose to healthy tissue.

That claim is now being tested in bigger studies. Early data in soft tissue sarcoma, head and neck cancer, and melanoma have been enough to draw interest, but they are not the final answer.

But promising ideas are common in oncology. What matters is survival in larger trials, so the focus has moved from mechanism to evidence. Can the benefit be reproduced? Can it extend across tumor types? And can the immune effects seen so far lead to better outcomes for patients?

References and Further Reading

1. About Nanobiotix. Bionity. [Accessed April 2026] https://www.bionity.com/en/companies/1034923/nanobiotix.html
2. Nanobiotix. Linkedin. [Accessed April 2026] https://www.linkedin.com/company/nanobiotix/about/
3. Nanobiotix strengthens its NanoXray pipeline with the launch of NBTX-TOPO development, the first nanotherapeutic with embedded radar. (2013). Nanobiotix. [Accessed April 2026] https://ir.nanobiotix.com/system/files-encrypted/nasdaq_kms/news/2022/01/07/8-54-53/Scientific%20Clinical%20_%20Nanobiotix%20strengthens%20its%20NanoXray%20pipeline%20with%20the%20launch%20of%20NBTX-TOPO%20development%2C%20the%20first%20nanotherapeutic%20with%20embedded%20radar.pdf
4. NANORADIOENHANCER PLATFORM. Nanobiotix. [Accessed April 2026] https://nanobiotix.com/our-science/nbtxr3/
5. Bienassis, C. et al. (2025). The radioenhancer NBTXR3: Bridging physics and biology to improve radiotherapy outcomes and prime anti-tumor immunity. Journal of Experimental & Clinical Cancer Research: CR, 44, 320. DOI:10.1186/s13046-025-03579-1, https://link.springer.com/article/10.1186/s13046-025-03579-1
6. Darmon, A. et al. (2022). Radiotherapy-activated NBTXR3 nanoparticles modulate cancer cell immunogenicity and TCR repertoire. Cancer Cell Int 22, 208. DOI:10.1186/s12935-022-02615-w, https://link.springer.com/article/10.1186/s12935-022-02615-w
7. Chen, X. et al. (2025). Molecular mechanisms underlying the abscopal effect induced by radiotherapy and its synergistic translational potential with immunotherapy. Therapeutic Advances in Medical Oncology, 17, 17588359251387534. DOI:10.1177/17588359251387534, https://journals.sagepub.com/doi/10.1177/17588359251387534
8. NANOBIOTIX Announces Updates to JNJ-1900 (NBTXR3) Clinical Program Following Transfer of Ongoing Phase 3 Head and Neck Cancer Trial Sponsorship and Operational Control. (2025). EuroNext. [Accessed April 2026] https://live.euronext.com/en/products/equities/company-news/2025-10-24-nanobiotix-announces-updates-jnj-1900-nbtxr3-clinical
9. NANOBIOTIX ANNOUNCES FIRST EVER RADIOENHANCER TO RECEIVE EUROPEAN MARKET APPROVAL. (2019). MassBio. [Accessed April 2026] https://www.massbio.org/news/member-news/nanobiotix-announces-first-ever-radioenhancer-to-receive-european-market-approval/
10. NANOBIOTIX Announces Updated Phase 1 Results Continuing to Support JNJ-1900. (2025). Globe News Wire. [Accessed April 2026] https://www.globenewswire.com/news-release/2025/09/29/3158214/0/en/NANOBIOTIX-Announces-Updated-Phase-1-Results-Continuing-to-Support-JNJ-1900-NBTXR3-Plus-Anti-PD-1-as-a-Potential-New-1L-or-2L-Option-in-Anti-PD-1-Na%25C3%25AFve-or-Resistant-R-M-HNSCC.html
11. Tourneau, C. L. et al. (2026). Intratumoral Radioenhancer Nanoparticle NBTXR3 Followed by Radiotherapy in Head and Neck Cancer: A Phase 1 Dose-Expansion Nonrandomized Clinical Trial. JAMA Otolaryngology - Head & Neck Surgery, e254939. DOI:10.1001/jamaoto.2025.4939, https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2844257
12. NANOBIOTIX Announces New Results From a Phase 1 Study Evaluating JNJ-1900 (NBTXR3) in Combination With Immune Checkpoint Inhibitors as a 2L+ Therapy for Patients With Primary Cutaneous Melanoma Resistant to Anti-PD-1. (2025). EuroNext. https://live.euronext.com/en/products/equities/company-news/2025-09-17-nanobiotix-announces-new-results-phase-1-study-evaluating
13. NANOBIOTIX Announces License Agreement for Worldwide Co-development and Commercialization of Potential First-In-Class Radioenhancer NBTXR3. (2023). BioSpace. [Accessed April 2026] https://www.biospace.com/nanobiotix-announces-license-agreement-for-worldwide-co-development-and-commercialization-of-potential-first-in-class-radioenhancer-nbtxr3

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