Production and molecular design of recombinant proteins for functional modulation of biomolecular corona effects: Individual Research Project

In DIRNANO we believe in the potential of nanoparticles (NPs) to revolutionize the diagnosis, treatment, and prevention of the most challenging human diseases, such as cancer and neurodegeneration. The size and chemical complexity of nanomaterials makes them ideal tools for precision medicine. That is, targeting the drug to the specific site of action, avoiding the complications of pharmacological side effects. However, newly developed nano-products seldom reach the market. One of the main reasons underlying this issue is the activation of the innate immune system upon NPs administration, which lead to NP clearance through phagocytosis, acute inflammation/coagulation, and NP-specific antibody production. 

The NP's protein Corona

An important factor influencing the interface between NP and immune system is the so-called NP’s protein corona. The protein corona is a layer of molecules (e.g., serum proteins) that forms around the NPs when they are introduced into the biological fluid. Once it is formed, the protein corona is stable overtime and is known to play a central role in determining the fate of NPs in the organism. The composition of protein corona varies for different nanoparticles and therefore, a better understanding of its composition and mechanism of formation could help us modulate immune reactivity towards the NPs. 

Within these contexts, the ESR-3 in her project aims at engineering and producing  plasma proteins – such as elements of the innate and adaptive immune response or coagulation factors – with manipulated binding avidity and transducing effects. It is expected that, the resulting protein constructs will not only serve to study the binding mechanisms but could also be used to create a pre-made corona that would compete with the natural proteins. The surface functionalized NPs with engineered proteins will be then investigated in terms of their ability to cause innate immune activation, especially the activation of complement system, neutrophiles, basophils, monocytes and platelet responses.

 

Cristina Fontecha Cuenca - Early Stage Researcher

Department of Biomedical Science - Università degli Studi di Padova (Italy)

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This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 956544
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