‘Protein corona’ is the term used to define the outer layer of endogenous proteins that forms on the surface of nanoparticles as soon as they contact with biological fluids. Despite being overlooked for several years, this is the first step that affects nanoparticle pharmacokinetics and clearance by the mononuclear phagocyte system. However, reliably understanding nanoparticle-protein interactions and how the subsequent corona influences their fate relies on choosing appropriate methodology and protein source. This work demonstrates the importance of using species-specific and fit-for-purpose materials when studying the formation of the protein corona and respective functional effects. Using human serum, we show that poly(2-oxazoline)-coated nanoparticles exhibit a completely different behaviour compared to non-human models, being selectively uptaken by dendritic cells. Furthermore, we identify two different components mediating this uptake, namely the complement system and type A scavenger receptors, competing with naturally occurring oxidized LDL. Then, by using different MXenes, we show how the constitution of corona can be directly correlated with effects on the intrinsic coagulation system and the complement pathways. Finally, we illustrate the need for improving and standardizing methodology with two case studies. Ultimately, our findings reveal that studying the protein corona using relevant models is crucial, and neglecting it can lead to misinterpretation of in vitro screenings.

L'impatto della corona proteica sulla cattura e la funzionalità delle nanoparticelle

MAGALHAES VELOSO, PEDRO RAFAEL
2025

Abstract

‘Protein corona’ is the term used to define the outer layer of endogenous proteins that forms on the surface of nanoparticles as soon as they contact with biological fluids. Despite being overlooked for several years, this is the first step that affects nanoparticle pharmacokinetics and clearance by the mononuclear phagocyte system. However, reliably understanding nanoparticle-protein interactions and how the subsequent corona influences their fate relies on choosing appropriate methodology and protein source. This work demonstrates the importance of using species-specific and fit-for-purpose materials when studying the formation of the protein corona and respective functional effects. Using human serum, we show that poly(2-oxazoline)-coated nanoparticles exhibit a completely different behaviour compared to non-human models, being selectively uptaken by dendritic cells. Furthermore, we identify two different components mediating this uptake, namely the complement system and type A scavenger receptors, competing with naturally occurring oxidized LDL. Then, by using different MXenes, we show how the constitution of corona can be directly correlated with effects on the intrinsic coagulation system and the complement pathways. Finally, we illustrate the need for improving and standardizing methodology with two case studies. Ultimately, our findings reveal that studying the protein corona using relevant models is crucial, and neglecting it can lead to misinterpretation of in vitro screenings.
15-apr-2025
Inglese
PAPINI, EMANUELE
Università degli studi di Padova
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/215652
Il codice NBN di questa tesi è URN:NBN:IT:UNIPD-215652