Nanoparticles in the Biological Context: Surface Morphology and Protein Corona Formation

Abstract

A recent paper demonstrated that the formation of a protein corona is not a general property of all types of nanosized objects. In fact, it varies between a massive aggregation of plasma proteins onto the nanoparticle down to traces (e.g., a few proteins per 10 nanoparticles), which can only be determined by mass spectrometry in comparison to appropriate negative controls and background subtraction. Here, differences between various types of nanosized objects are discussed in order to determine general structure–property‐relations from a physico‐chemical viewpoint. It is highlighted that “not all nanoparticles are alike” and shown that their internal morphology, especially the difference between a strongly hydrated/swollen shell versus a sharp “hard” surface and its accessibility, is most relevant for biomedical applications.

Effect of Core‐Crosslinking on Protein Corona Formation on Polymeric Micelles

“…[ 11,12 ] The more and more widespread use of micelles in the field of nanomedicine may result from the fact that especially micelles seem to have reduced interactions with proteins and are stable in plasma, which is a requirement for a successful application as drug delivery system. [ 13–18 ]…”

“…[ 7,25–28 ] Throughout all the nanoparticles, which were characterized regarding pronounced protein corona formation, most were colloids or “hard” nanoparticles with a sharp hydrophobic and/or charged surface. [ 18,29–31 ] For these types of nanoparticles, this interphase dominates the interaction with plasma proteins. [ 17,18,32–34 ] For example, polystyrene nanoparticles typically acquire a thick and tightly bound protein layer around the nanoparticle, which is also termed “hard protein corona.” [ 35–37 ] This happens because a sharp and distinct surface can induce a change of the conformation (denaturation) of plasma proteins [ 38 ] in order to increase the interactions with the hydrophobic and charged surface.…”

“…Here, it is interesting to consider work on colloids from polystyrene (PS), which are stabilized with various (also PEGylated) detergents. [ 18 , 39–41 ] In this case, the surface will—on average—also be coated with hydrophilic polymers (PEG), but due to the dynamic exchange of the detergents (unimers in equilibrium with micelles, critical micelle concentration, CMC), parts of the hydrophobic surface will also get constantly accessible to proteins under equilibrium conditions as discussed in [ 18 ] . An extensive corona formation from plasma proteins would be the result in this case.…”

Polymer-based nano-therapies to combat COVID-19 related respiratory injury: progress, prospects, and challenges

“…Once the nanocarriers reach the blood circulation inside the body, they can interact with proteins to form protein corona. [ 198 ] Other complications may appear when nanoparticles enter blood circulation due to the complex matrix containing ions, small molecules, proteins, and cells in the circulation. [ 199 ] Thus, the characterization of protein corona is a vital step to be investigated during polymeric nanomedicine development to treat COVID-19 related complications including respiratory injury.…”

Irreversible Adsorption of Serum Proteins onto Nanoparticles

“…The fate of nanoparticles in a biological setting, such as recognition as a foreign body by the organism or controlling the mechanisms and kinetics of cellular uptake, is believed to be largely governed by the proteins adsorbing onto the particles upon contact with a biofluid. [1] This dynamic protein layer, often referred to as the protein corona, can be divided into an inner layer of strongly adsorbed proteins (hard corona) as well as an outer layer of more loosely bound proteins (soft corona). [2] Supporting Information, along with the detailed synthesis procedures.…”