As nanomedicine and nanoparticle-based formulations pave the way for a new generation of pharmaceutics, a deeper understanding of the underlying mechanisms and in vivo interactions is critical to optimize them as best as possible.
It has been found that nanoparticles, once in contact with bodily fluids, interact with the many different biomolecules present. As a result of this interaction, proteins might bind specifically to the surface of these nanoparticles, forming a layer of endogenous proteins. This layer is called the protein corona and it has a significant impact on the fate of the particles inside the body, including in the activation, or evasion, of immune system cascades.
The protein corona is dependent on the different characteristics of the particles, including their size, surface charge, shape, nature and its coating. With this in main, the main objective of ESR 2 lies on investigating the relationship between the coatings of different nanoparticles and the respective protein corona that forms once in contact with animal serum. By performing different corona analysis in different formulations, ideally, ESR 2 would be able to establish molecular patterns responsible for interacting with specific proteins, in turn allowing a more detailed design depending on the desired effect.
A particular case is the comparison between poly(ethylene glycol) (PEG) and poly(2-methyl-2-oxazoline) (PMOXA). PEG is considered the “gold standard” in nanoparticle coating since it largely increases circulation time by avoiding macrophage uptake; this effect is corroborated by protein corona studies, that show a reduction in the adsorption of blood proteins. In the case of PMOXA, protein corona studies show a strong opsonization by the complement protein C3, which translates into an accelerated capture by macrophages.
The establishment of these relationships between the coatings, the protein corona and the in vivo effect could help designing formulations that avoid immune detection – which could be a very useful tool in designing new nanoparticles for cancer therapies – or formulations that cause a pro-inflammatory effect – which could improve the efficacy of vaccine nanotechnology.
Lastly, the project also predicts testing the formulations with the serum from different organisms, such as pig and mice serum. The main goal of these tests is to determine how reliable the use of these animal models is, providing even further insight regarding nanoparticle formulations and the protein corona.
Pedro Rafael Magalhães Veloso - Early Stage Researcher
Department of Biomedical Sciences - Università degli Studi di Padova (Italy)