Marie Morille: The Mega-Strategic Nanoformulation

When Marie Morille talks about her research on nanovectors and biotherapies, it sounds like something out of a science-fiction story. Injecting microparticles that carry nanoparticles—which themselves contain messenger RNA—through the body… This basic research at the Charles Gerhardt Institute (ICGM) offers a glimpse into the medicine of the future and the development of tomorrow’s biomedicines. One of her research areas focuses specifically on treating osteoarthritis with cell therapy. When injected into the joint, stem cells can differentiate into cartilage cells to repair the cartilage. The challenge, therefore, is to successfully control this differentiation.

How? Through a complex system based on collagen microspheres, which serve both as a scaffold for stem cells and as a reservoir for nanoparticles containing nucleic acids that control differentiation. Her work in this field of nanomechanics involves first developing effective nanovectors capable of entering cells, and then modifying the surfaces of the particles to control their attachment and the timing of the release of these nanosystems. And while proof of concept is the goal,“this research is still very basic, ”acknowledges the expert in nanoformulations.

The new mascot of biomedicine

This research is a natural extension of his postdoctoral work at the Institute of Regenerative Medicine and Biotherapies (IRMB), which preceded his appointment as an associate professor at the University of Montpellier in 2012. This provided an opportunity to produce initial findings on cartilage repair as part of a project Inserm Transferproject. The researcher optimized the formulation of a protein used to promote cell differentiation into cartilage, a result patented in 2012. The promising results tested in mice led to an application a few years later by the company Normandie Biotech.“The treatment was used in veterinary medicine on racehorses. It was a pleasant surprise to see such a rapid application,” says Marie Morille.

His early research on nanoparticles dates back to his doctoral studies. His goal at the time was to promote the accumulation of these carriers—used to transport nucleic acids (DNA)—in cancer cells, the targets of the treatment.“We coat the surface of these nanoparticles with polymers to ensure their stability after intravenous injection. The system is then more likely to accumulate in tumors through a phenomenon known as the EPR (enhanced permeability and retention) effect, which relies, among other things, on the imperfect nature of the blood vessels supplying the tumors,” explains the researcher.

Interest in this mechanism, which was a major focus during her doctoral research between 2006 and 2009, has since waned.“While the effects were clearly demonstrated in mice, they have not been conclusive in humans,”notes the researcher, who is now working on the new darling of biomedicine: extracellular vesicles (EVs). Secreted by cells, these vesicles are ideal nanovectors for delivering drugs because they are naturally equipped to enter cells. They also show promise for applications in regenerative medicine due to their intrinsic properties, particularly their anti-inflammatory effects.“We just need to figure out how to harness them,” explains Marie Morille.

A highly competitive sector

His new research project therefore focuses on finding a way to stabilize them so they can be used in treatments.“For example, by modifying the surface of these vesicles with polymer molecules, we aim to preserve their physical integrity and biological activity. We have even developed freezing and freeze-drying methods to facilitate their use, and we are currently testing, in collaboration with the Montpellier Cancer Research Institute (IRCM), testing their radiolabeling to track them within the body. We are also interested in their potential for delivering another type of biotherapy: intracellular antibodies, also in collaboration with the IRCM,” explains the researcher.

Launched in 2016, this research enabled her to secure junior ANR funding in 2020 and to be named an IUF (Institut Universitaire de France) fellow in 2022. This time, her project focused on pulmonary treatments. The Ve particles have the advantage of not getting stuck in mucus, unlike synthetic nanovectors. A property that improves treatment efficacy.“Thanks to a significant reduction in my teaching load, this IUF grant gives me the time to work—a necessity because research moves quickly in this highly competitive field,” acknowledges the associate professor, who nevertheless does not neglect the teaching aspect of her work.

California Dreamin'

With two major educational initiatives: the creation of a dedicated nanoparticle equipment platform as part of the BioOc program—a project selected in 2022 through the “Skills and Professions of the Future ” France 2030; and her participation, as co-educational lead, in the Immune4Cure University Hospital Institute project led by C. Jorgensen. And as if all that weren’t enough, Marie Morille is preparing for a year-long exchange in September at the University of California, Davis, in Sacramento.  “This is a pivotal moment in my career—very busy but also very exciting,” concludes the tireless researcher.