Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
The Biam and the Institut Frédéric-Joliot are advancing our knowledge about the importance of the nature of protein coronas on nanoparticle toxicity. Their results reveal a new concept: the protein interactome, as applied to the corona of nanoparticles.
Magnetic silica nanoparticles hold promise for medicine, with roles as drug-specific vectors, contrast agents for medical imaging, or physical treatment agents in oncology. Nanoparticles coupled with drugs could be directed to a diseased organ in order to locally deliver low-dose therapeutic molecules, thus avoiding side effects. Nevertheless, when these nanoparticles circulate in the body, they inevitably attract proteins present in the biological environment to their surface, thus surrounding themselves with a protein corona whose composition varies according to their nature and environment. This corona modifies their properties and their fate within the body. In particular, it leads to their rapid elimination by macrophages.
The latest-generation proteomics, based on ultra-high-performance mass spectrometers, allows the thorough characterization of the composition of these coronas. By studying the composition of these coronas according to the environment in which they are placed, as well as the dynamics of their formation, the researchers demonstrated that the environment used in classic in vitro tests could have a direct impact on their toxicity. Indeed, compared to a corona of bovine proteins, a corona of human proteins considerably reduces the toxicity of silica nanoparticles for human liver cells. However, fetal calf serum is conventionally used for these in vitro tests. This leads us to believe, under these conditions, that these tests overestimate the toxicity of nanoparticles and that better compositions must be found.
By studying the dynamics of corona formation, these researchers have demonstrated that nanoparticles quickly adsorb proteins for which they have physicochemical affinities. Nevertheless, these proteins in turn trap new proteins that they interact with in the course of time, creating a true functional network.
Exploiting the innovative concept of a "protein interactome applied to the corona of nanoparticles" may lead to more rational proposals to explain the toxicity of nanoparticles. Finally, this concept could make it possible to design nanomedicines with a pre-determined protein corona in order to make them less noticeable to the immune system (and thus more stealthy), and also to reach their tumor target more effectively.
The species origin of the serum in the culture
medium influences the in vitro toxicity of silica nanoparticles to HepG2 cells
| PLoS One, Experimental separation steps influence the
protein content of corona around mesoporous silica nanoparticles | Nanoscale, The timeline of corona formation around silica
nanocarriers highlights the role of the protein interactome | Nanoscale
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.