By Laurent Levy

If you know anything about Nanobiotix, then you may have read about the lead product candidate in our pipeline, NBTXR3. NBTXR3 is a potential first-in-class, solid tumor-agnostic, therapeutic combination-agnostic radioenhancer composed of hafnium oxide nanoparticles that may help millions of people diagnosed with cancer.

But what does this all mean? A radioenhancer composed of hafnium oxide nanoparticles? What, exactly, is a nanoparticle? And why is hafnium oxide Nanobiotix’s nanoparticle of choice? I’ll break things down for you. But first, let’s take a little journey (and I do mean little!) back in time, so we’re all on the same page about what it means to work in the nanoscale.

Get ready, get set, let’s go nano.

Nanotechnology, Nanomaterials, and Nanoparticles

The term “nanotechnology” was coined in 1974 by scientist Norio Taniguchi to reference the understanding and manipulation of matter at nanoscale. This matter, called “nanomaterial,” is between 1 and 100 nanometers, or about one-billionth the size of a meter.

Unless you’ve studied physics, it may be hard to imagine just how small this really is. But in the 1980s, that didn’t stop many science-fiction writers from playing around with the idea of assembling nanomaterials and releasing them into their narratives — often as forces of destruction. In Stanislaw Lem’s novel, Peace on Earth, a swarm of tiny robots — each the size of a speck of dust — was sent to Earth by artificial intelligence to destroy all human-made weapons, software, and modern technology.

The science in most nano-inspired stories is deeply flawed. First, as a nanophysicist, I must say that nanotechnologies are much, much smaller than a speck of dust. Second and more importantly, even if we overlook the scientific inaccuracies, we believe that the things we create at nanoscale will create a better future for humanity, rather than one that is dystopic.

But these storytellers were working with intriguing questions that I’ve grappled with during my career: How can we use nanomaterials, the building blocks of nanotechnology, to reshape our lives for the better? And how could one application of nanotechnology — a nanoparticle composed of hafnium oxide — potentially revolutionize treatment for millions of patients with cancer?

Nanophysics: An “Alchemy” That Actually Changes the Elements

It’s hard to imagine how infinitesimally small things are at nanoscale. But it’s perhaps even more difficult for people to wrap their heads around the idea that the properties of nanomaterials, such as melting point, electrical conductivity, magnetic permeability, and chemical reactivity, are drastically different from those of their larger particle counterparts.

Yet even before people had a modern understanding of physics and nanophysics, they seemed to intuit that it could be possible to fundamentally change elements. In Europe’s medieval period, some people subscribed to the discipline of “alchemy” — a mélange of mysticism, philosophy, and the best science of the time — to try to combine common substances to create potions that could cure disease, forge precious metals, and even attain eternal life.

To my knowledge, no alchemist has ever achieved these lofty ambitions, but today’s nanophysicists can change the properties of natural elements and design nanoparticles by changing their size. For example, gold nanoparticles aren’t actually gold in color, but are instead purple, red, orange, or even brown. This is because the electrons of these nanoparticles are closely confined at nanoscale, which restricts their movement. This causes the nanoparticles to react to light differently than larger gold particles — the color depends on their exact size and shape.

Beyond just their color, nanoparticles are “tunable” in that they can be designed with different functional properties (electrical conductivity, chemical reactivity, etc.). It’s a little like tuning a guitar: You can make subtle turns to its tuning pegs to produce different sounds from the instrument.

Hafnium Oxide: A Nanoparticle That Is Its Own Medicine

Now, here’s where it gets really exciting. Rather than simply discovering cool new properties for nanoparticles made of various elements, what if we used them as a therapeutic option? This is exactly what I’ve been working on for nearly two decades with the team at Nanobiotix. We set out to discover how to apply nanoparticles (i.e., “Nano”) to human biology (i.e., “Bio”) and develop therapeutics (i.e., “Tix”) that could improve treatment outcomes for patients with major diseases. Since we embarked on this journey, we have invented several nanoparticle platforms that address a variety of different diseases, including our potential first-in-class radioenhancer, NBTXR3, which is made of modified hafnium oxide.

On the periodic table of elements, hafnium has a high atomic number, meaning that each hafnium atom contains a large number of electrons. In oncology, radiotherapy – a common form of treatment – functions by directing a high-energy beam at solid tumors. This beam causes the electrons within the tumor cells to “jump” off the atoms where they are contained and kill the cells around them. Unfortunately, because electrons are present in the atoms of tumor cells and healthy cells alike, radiotherapy can also damage the healthy cells that surround the tumor.

Our hypothesis at Nanobiotix was that by introducing hafnium oxide nanoparticles into solid tumor cells prior to radiotherapy, thereby packing the area with many more electrons, we could increase the damage within the tumor without increasing damage to surrounding healthy tissue.

We designed NBTXR3 as an injectable substance that could be administered to any solid tumor that can be reached by a needle. We achieved our European CE marking for NBTXR3 under the brand name Hensify® to treat soft tissue sarcoma and are currently working to develop the product candidate across any solid tumor type where radiotherapy is part of the treatment regimen. We have also discovered that the tumor cell destruction caused by NBTXR3 may also have an “immune priming” effect, activating several immune pathways that allow the immune system to identify and attack tumor cells. This could allow NBTXR3 to be combined with cancer immunotherapies to potentially help patients with metastatic cancers as well.

Contrary to what some dystopian science-fiction writers might have you believe, our ability to start taking control of the material world at nanoscale may have major medical implications as we continue to uncover new ways to improve treatment outcomes for cancer patients around the world. With the hafnium oxide-packed NBTXR3 in the lead, Nanobiotix remains committed to the promise of nanotechnology.