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Posted: Jun 03, 2014
Personalized protein coronas result in different therapeutic or toxic impacts of identical nanoparticles
(Nanowerk Spotlight) When nanoparticles enter a physiological environment, such as blood, they come into immediate contact with various biomolecules, such as proteins. These biomolecules form a coating layer on the nanoparticle surface, thereby imparting a unique biological identity to the nanoparticle, which could be very different from the pristine nanoparticle surface.
The layers of proteins adsorbed to the surface of a nanomaterial at any given time is known as the protein corona. The formation of protein corona is a continuous state of flux in which many proteins compete to bind to the nanoparticle surface, each with their own characteristics such as concentration, structure and solubility determining their final affinity to the nanoparticle surface.
This is the reason why biological responses to nanoparticles are strongly dependent to the type and amount of associated proteins in the composition of the protein corona (read more: "Proteins interact with 'ultrasmall' nanomaterials in unique ways"). The protein corona determines the biological fate of nanoparticles and physiological responses.
New research findings now show that the plasma protein alterations associated with different diseases, medical conditions, or even lifestyle, can affect the protein composition and content of the hard corona composition.
These findings indicate that different individuals may have a personalized protein corona owing to their distinct type, severity and period of disease, heterogeneity, individual genetic variations and environmental factors.
This means that exactly the same nanoparticles may have different therapeutic and/or toxic impacts on different individuals.
Schematic of the personalized protein corona from different diseases/states. Plasma alterations in different diseases/medical conditions may affect the protein adsorption on the nanoparticle surface, leading to the formation of a personalized protein corona for each patient. Many proteins are associated with the protein corona for different patients, while some proteins only appear or disappear in the hard corona for particular diseases. (Reproduced by permission of The Royal Society of Chemistry) (click image to enlarge)
"Our results demonstrate that the type of disease has a crucial role in the protein composition of the nanoparticle corona," Morteza Mahmoudi, a professor at Tehran University of Medical Sciences, who heads the >Laboratory of Nano-Bio Interactions, tells Nanowerk. "Based on these results, we introduce the concept of the 'personalized protein corona' (PPC) as a determinant factor in nano-biomedical science. This study will help researchers rationally design experiments based on the 'personalized protein corona' for clinical and biological applications."
In contrast to the current view, which assumes that the protein composition/content of coronas from different individuals is the same and, hence, that the data obtained from each patient can be generalized to others, this new research demonstrates that different patients may have personalized protein coronas which are different from each other.
Whereas so far scientists have focused on the effects of the physicochemical properties of nanoparticles on protein corona formation, this new study suggests that the personalized plasma alterations that occur during different diseases or conditions also need to be considered.
"Indeed", as Mahmoudi emphasizes, "the adsorption of plasma proteins on the nanoparticle surface is a multi-factorial process in which the plasma protein alterations play a determinant role in the formation of protein corona."
To check their hypothesis that different diseases or medical conditions may affect the competitive binding of proteins to the surface of nanoparticles, the team incubated two different hydrophobic/hydrophilic types of nanoparticles (polystyrene and silica) with the plasma from age and sex-matched human subjects with different diseases (e.g., breast cancer, diabetes, hypercholesterolemia, rheumatism, fauvism, smoking, hemodialysis, thalassemia, hemophilia A and B, pregnancy, common cold and hypofibrinogenemia).
As some plasma proteome differences are attributed to the gender and age of the patients, only the samples from age and sex-matched patients who had only one disorder causing plasma alteration was collected.
"Our results show that changes in the plasma protein composition due to disease alter the nanoparticle hard corona composition, which in turn gives the nanoparticles an unpredictable biological identity – compared to the current in vitro data, which do not consider the plasma alteration effect – that determines their biological fate," says Mahmoudi. "Notably, the association of multiple disorders can also affect the composition of the hard corona. In addition, the data demonstrate that the composition of the hard corona varies among healthy individuals, as well as among patients with various diseases/medical conditions."
These findings open a new avenue towards the design of safe and high yielding nanoparticles for specific patients. The team's introduction of a personalized protein corona concept as a key factor at the nanobiointerface could provide a novel approach for applying nanomedicine to personalized medicine, improving diagnosis and treatment of different diseases tailored to the specific conditions and circumstances of individual patients.