Conference Dr. Florence Gazeau

Dr. Florence Gazeau

NABI (Nanomedecine, Biologie Extracellulaire, Intégratome et Innovations en Santé), CNRS- INSERM- Université Paris Cité

Metallic nanoparticles, a new ally in immunobiotherapies

Harnessing the immune system to combat cancer has become one of the most transformative directions in modern medicine. While immunotherapies such as CAR T cells and immune checkpoint inhibitors have achieved remarkable success in hematological malignancies, their translation to solid tumors remains a major challenge. This limitation is largely driven by the immunosuppressive tumor microenvironment and by physical barriers—such as dense, fibrotic stroma—that restrict immune cell access and function. Addressing these obstacles requires new tools capable not only of activating immune responses, but also of monitoring, guiding, and dynamically reprogramming them in vivo.

In this context, magnetic and plasmonic nanoparticles offer a uniquely versatile platform at the interface of physics, materials science, and immuno-oncology. In this lecture, I will discuss how iron oxide–based and gold-functionalized magnetic nanomaterials can be leveraged—alone or in combination with external stimuli such as magnetic fields or light—to both track and control immune responses with high spatiotemporal precision.

First, I will demonstrate how iron oxide nanoparticle labeling enables the non-invasive tracking of CAR T cells by MRI over extended periods in vivo. Beyond imaging, magnetic actuation provides a means to actively guide these cells toward tumors, significantly enhancing their infiltration and therapeutic efficacy. This dual imaging–actuation capability illustrates the power of magnetic nanoparticles as both diagnostic and therapeutic agents (1).

Second, I will present a high-throughput screening platform designed to evaluate the immunomodulatory properties of metallic nanoparticles and ions. By integrating laser activation with advanced data analysis, we uncover switchable macrophage polarization states, enabling controlled transitions from immunosuppressive to pro-inflammatory phenotypes. These findings open new avenues for designing stimuli-responsive nanomaterials that precisely tune immune function (2).

Third, focusing on highly fibrotic tumors such as cholangiocarcinoma, I will show how magnetic-plasmonic nanostructures can be used in combinatorial therapies. Photothermal activation of gold-decorated iron oxide nanoflowers, coupled with PD-1 checkpoint blockade, remodels the tumor stroma, reduces mechanical stiffness, and promotes immune cell infiltration. This approach effectively converts immune-resistant “cold” tumors into “hot,” responsive ones, highlighting the potential of nanotechnology to overcome key barriers in solid tumor immunotherapy (3).

Finally, I will explore the emerging field of extracellular vesicle–based therapies. By using magnetic nanoparticle preconditioning, we generate vesicles that are both MRI-visible and magnetically responsive, enabling their tracking and remote functional modulation. These engineered vesicles exhibit enhanced immunoregulatory activity, which can be further amplified under magnetic stimulation, offering a new paradigm for cell-free, controllable immunotherapies (4).

Altogether, this work positions metallic nanoparticles not merely as passive carriers, but as active, multifunctional agents capable of sensing, guiding, and reprogramming immune responses. I will conclude by discussing the opportunities and challenges for translating these approaches toward clinical applications, and the broader role of nanotechnology in shaping the future of precision immunotherapy (5).

References

(1) In Vivo Monitoring and Magnetically-Enhanced Delivery of CAR T-Cells to Solid Tumor. Huan Chen, Alice Machado, Dongjie An, Sonia Becharef, Gwennhael Autret, Dmitry Ayollo, Sarah Razafindrakoto, Philippe Nizard, Florent Carn, Yun Luo, Frédéric Pendino, Claire Mangeney, Jelena Kolosnjaj-Tabi, Emmanuel Donnadieu, Florence Gazeau. Advanced Functional Materials, 2024.
https://doi.org/10.1002/adfm.202414368

(2) Multivariate Screening and Automated Clustering of Macrophage Immunoreactome to Nanoparticles and Photothermal Therapy. Sonia Becharef, Léa Jabbour, Nassima Bekaddour, Giulio Avvedutto, Nathalie Luciani, Gautier Laurent, Rana Bazzi, Edouard Alphandery, Stéphane Roux, Amanda K. A. Silva, Kelly Aubertin, Jean-Philippe Herbeuval, Florence Gazeau
Advanced Science 2025 Aug;12(31):e2405860. doi: 10.1002/advs.202405860

(3) Laser-activated nanoparticles rewire tumor microenvironment enhancing PD-1 blockade and T cell response in cholangiocarcinoma.
Mirko Minini, Giulio Avveduto, Sonia Becharef, Marie Meunier–Thaens, Bouchra Lekbaby, Maria Perez-Lazon, Alice Machado, Thomas Guilbert, Julie Lesieur, Gilles Renault, Sara Ceccacci, Ida Chiara Guerrera, Christophe Klein, Jérémy Augustin, Rana Bazzi, Stephane Roux, Jonathan Pol, Emmanuel Donnadieu, Florence Gazeau, Laura Fouassier. Hepatology, DOI: 10.1097/HEP.0000000000001545

(4) Magnetic nanoparticle priming of mesenchymal stromal cells generates MRI-detectable extracellular vesicles with enhanced immunomodulatory activity
Lea Jabbour, Estelle Surply, Sonia Becharef, Sarah Razafindrakoto, Nathalie Luciani and Florence Gazeau, submitted.

(5) Nanomedicine Meets Immunotherapy: Advancing Adoptive Cell Therapy with Nanoparticles in the Treatment of Cancer with Sustainability Perspectives. Erica Frostegård, Tatiana Bobrova, Amalie Leinebø, Thibault Leray, Shayamita Ghosh, et al..Advanced Science, 2026, pp.e22864. doi :10.1002/advs.202522864