The Protein Corona Conundrum: Exploring the Advantages and Drawbacks of its Presence around Amphiphilic Nanoparticles

Abstract

The success of targeted drug delivery systems still requires a detailed understanding about the biological consequences of self-developed biomolecular coronas around them, since this is the surface that interacts with living cells. Herein, we report the behavior of carbohydrate-decorated amphiphilic nanoparticles in a plasma environment with regard to the formation and biological consequences of the protein corona. Naked amphiphilic nanoparticles were produced through the self-assembly of azido-PEO 900 -docosanoate molecules, and the coupling of N-acetylglucosamine via click chemistry enabled the fabrication of the corresponding bioactive glyco-nanostructures. Light scattering measurements, sodium dodecyl sulfate−polyacrylamide gel electrophoresis, liquid chromatography−mass spectrometry, and the Pierce BCA protein assay all confirmed the presence of protein coronas around the self-assembled nanoparticles, regardless of the presence of the sugar residues, although it reduces the amount of adsorbed proteins. The protein coronas were formed mainly by human serum albumin, complement proteins, apolipoproteins, immunoglobulins, and proteins involved in the coagulation cascade (fibrinogen and prothrombin). While the presence of these protein coronas significantly reduced cellular uptake of the amphiphilic assemblies, they also notably reduced the cytotoxic and hemolytic effects that result from the contact of the nanoparticles with living cells. Accordingly, we highlight that protein coronas should not always be treated as artifacts that have to be avoided because they can also provide beneficial effects.

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“…Moreover, protein corona formation causes destabilization of the nanoparticles due to agglomeration of the particles, causing deleterious effects in the treatment regimen. [ 44 ] As a result. the stability of the nanoparticle system was also measured in a solution containing 10% human serum at 37 °C to mimic physiological blood conditions.…”

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“…The hydrodynamic radius was measured using dynamic light scattering for a period of 7 days while the nanoparticles were in storage conditions of 4°C; as seen in the graph in Figure 2D, we observe that the size and zeta potential is constant over 7 days with minimal fluctuation hence proving that the nanoparticles are indeed stable. During systemic circulation, studies have shown that nanoparticle destabilization may occur due to the adsorption of serum proteins on the surface of the nanoparticle system, termed as the protein corona effect 34 . To test out the stability of the MSNPs in physiological conditions, the nanoparticles were incubated in PBS with 10% human serum for 24 h, while their hydrodynamic size and surface charge (zeta potential) were measured at regular intervals.…”

“…During systemic circulation, studies have shown that nanoparticle destabilization may occur due to the adsorption of serum proteins on the surface of the nanoparticle system, termed as the protein corona effect. 34 To test out the stability of the MSNPs in physiological conditions, the nanoparticles were incubated in PBS with 10% human serum for 24 h, while their hydrodynamic size and surface charge (zeta potential) were measured at regular intervals. As seen in Figure 2E, the nanoparticle system is indeed stable in human serum, hence proving that it can be used in physiological conditions.…”

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“…Nanoparticles administered into the blood can interact nonspecifically with serum proteins and form a shell of protein, called the protein corona [39][40][41][42][43][44]. Protein corona formation is mainly mediated by coulombic and Van der Waals forces, hydrogen bonding, and hydrophobic interactions [45].…”