Hafnium oxide nanoparticle (NBTXR3) (NBTXR3)

NBTXR3 is a first-in-class radioenhancer composed of functionalized hafnium oxide (HfO2) nanoparticles designed to amplify the therapeutic effect of radiotherapy in solid tumors [1, 2]. These nanoparticles possess a high atomic number (Z=72), which allows them to absorb and deposit significantly more energy from ionizing radiation compared to biological tissues [2, 12]. Upon activation by X-rays, NBTXR3 generates a high density of secondary electrons and reactive oxygen species (ROS) within the tumor cells, leading to enhanced DNA damage and subsequent cell death [2, 3]. The mechanism is primarily physics-based, making it potentially applicable across a wide range of solid tumors regardless of their molecular profile [1, 5]. Beyond direct cytotoxicity, NBTXR3-mediated radiotherapy has been shown to induce immunogenic cell death, promoting the release of tumor antigens and damage-associated molecular patterns (DAMPs) that prime the immune system against the cancer [2, 7, 15]. This dual action not only improves local tumor control but also has the potential to trigger systemic anti-tumor immune responses, such as the abscopal effect [13, 15]. The nanoparticles are administered via a single intratumoral injection and are designed to remain localized within the tumor throughout the course of radiotherapy [1, 12].

Other names

NBTXR3Hafnium oxide nanoparticlesHfO2 nanoparticlesNanoradioenhancerNBTX-IVNBTX-TopoHafnium oxide

NBTXR3 functions as a radioenhancer through a physics-based mechanism. The hafnium oxide nanoparticles, which have a high atomic number (Z=72), are internalized by tumor cells via endocytosis. When exposed to ionizing radiation (X-rays), the high electron density of hafnium leads to increased photon absorption and the emission of secondary electrons (photoelectrons and Auger electrons). This results in a localized increase in energy deposition (up to 9-fold) and the generation of reactive oxygen species (ROS), which cause extensive DNA damage and cellular stress. This process triggers immunogenic cell death (ICD), characterized by the release of damage-associated molecular patterns (DAMPs) and tumor antigens, thereby activating a systemic anti-tumor immune response.