Séminaire / Seminar - Le nanomagnétisme appliqué à la médecine - Florence Gazeau

Jeudi 2 mai 2024 à 11 h

IMPMC - Sorbonne Université - 4 place Jussieu - 75005 Paris - Barre 22-23, 4e étage, salle 401

Florence Gazeau, Université Paris Cité, MSC Med, CNRS UMR7057

Abstract

Since the 2000s, gold nanoparticles have raised interest for their biomedical applications as imaging probes, drug delivery system or therapeutic photothermal agents. Nevertheless, the use of gold in medicine is much more ancient than the advent of nanomedecine. Gold has been used under various forms since antiquity as drugs and proven to be biologically active. Injection of gold salts or “chrysotherapy” has been proposed as a medical treatment for rheumatoid arthritis until the 1990s
when presumably less toxic and more efficient treatments emerged. However, the fate of gold in the body has been poorly investigated at the nanoscale. Gold nanoparticles were supposed to be undegradable in the organism because of their chemical inertness. Common belief is that gold nanoparticles remain endlessly intact in tissues. Unexpectedly, we revealed that gold nanoparticles are actually degraded by cells, with an active role of cell lysosome into this biodissolution. Furthermore, we point out that the released gold recrystallizes into biopersistent nanostructures. Interestingly, these degradation products are similar to previously observed gold deposits, called “aurosomes,” in human tissues of patients treated with gold salts, underlying a common metabolism between gold nanoparticles and ionic gold. We will discuss the intracellular metamorphosis of gold salts and nanoparticles in the organism and show how the intracellular local environment can drive the biomineralization of unique gold nanostructures.

More generally we will show how the cellular response to metals and metallic nanoparticles is primarily governed by their intracellular transformations. We have proposed a meta-analysis of the transcriptomic responses of human cells to nanoparticles and ions of various metals (titanium, iron, copper, zinc, silver, cadmium, platinum, gold), in order to identify the commonalities and differences between cell responses to these compounds. This analysis revealed that the chemical properties of metals are more important than their known biological functions (i.e., essential metals, toxicity) in governing the cell transcriptome. Particularly, we evidence that the response to nanoparticles is dominated by the response to the ions they contain.Finally, in response to mouse pulmonary exposure to MoS2 nanosheets, we show the importance of extracellular vesicles release and intracellular transformation of the nanosheets to resolve nanoparticle-induced inflammation.

References
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Unexpected intracellular biodegradation and recrystallization of gold nanoparticles.
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Transcriptomic Meta-analysis Study, ACS Nanoscience Au, 2022 https://doi.org/10.1021/acsnanoscienceau.2c00035
4. Ortiz Peña, N., Cherukula, K., Even, B., Ji, D.-K., Razafindrakoto, S., Peng, S., Silva, A.K.A., Ménard-Moyon, C., Hillaireau, H.,
Bianco, A., Fattal, E., Alloyeau, D. and Gazeau, F. (2023), Resolution of MoS2 Nanosheets-Induced Pulmonary Inflammation
Driven by Nanoscale Intracellular Transformation and Extracellular-Vesicle Shuttles. Adv. Mater., 35: 2305230.
https://doi.org/10.1002/adma.202305230