What is the corona?

Structural depictions of transferrin (TF) and the protein corona. Cartoonrepresentation of the (chicken) TF polypeptide

chain (protein database entry 1N04). Sketch showing a polymer-coated FePtnanoparticle covered by a monolayer of TF molecules.

Hard corona The term of hard corona defines the long-lived

equilibrium state representing a fingerprint of ananoparticle in a certain environment

NP–protein labeling strategies:

electrostatic attachment of protein

covalent attachment to the NP ligand

attachment of a protein cofactor on NP

direct linkage of amino acid on the NP core.

Several factors influence the corona composition Hydrophobicity

Size

Charge

Sequence

Topology

Reaction milieu

Hydrophobicity

Size

Effect of the NP size on the behavior of adsorbed lysozyme

Schematic for the interaction of RNase A with silica nanoparticles of different diameters

Size

Charge

Sequence

Sequence

Topology

Protein with several NP binding sites. NP attachment can inactivate the protein via denaturation or blocking of the active site.

Schematic for the interaction of RNase A with silica nanoparticles of differentdiameters

The DNA-nanoparticle interactions

a) Structure of NP1 scaffold and the DNA backbone

b) Transcription level as a function of DNA–NP1 stoichiometry

c) Binding of DNA through complementary oligonucleotidehybridization.

equilibrium constant

Schematic representation of the protein corona on a nanoparticle illustrating theexchange processes and equilibrium constants. The exchange rates are a complex functionof the affinity for the surface, curvature effects from the surface, and changes in thesurrounding milieu, and much work is needed to evaluate the equilibrium constants underdifferent conditions.

What dose the cell see?

Nanoparticle–protein complexes as seen by the cell. Immediately on contact with biologicalfluid, nanoparticles take on a corona of proteins (red–yellow α-helices and red–blue β-sheets) that exchange with their surroundings. Proteins that reside on the nanoparticlesurface for much longer can be identified by cells. uptake of a nanoparticle–proteincomplex by cells depends on whether the cell membrane has receptors for the proteins,whether the proteins are presented in the correct orientation to interact with the receptor,and whether the nanoparticle-bound protein can compete effectively with the free proteinfor the receptor.

Separation

Size-exclusion chromatography study of nanoparticle-protein interactions. Theelution time of proteins is shifted depending on their affinity for the nanoparticlesurface, the longer the protein is associated with the nanoparticle the earlier theprotein elutes from the column. Proteins that have sufficiently long residencetimes elute in the void volume with the nanoparticles. It is clear that eachfraction collected from the size-exclusion column contains many differentproteins, which can be further separated by gel electrophoresis using denaturingacrylamide gels as shown on the right. The different gel bands can be cut outand the proteins identified by mass spectrometry.

Dose the NP always unfold proteins?

Schematic representation of artificial molecular chaperones

Applications

Schematic representation of nanoparticle-assistedmultimodality imaging techniques with their new multi-tasks applications for (A) MRI/optical imaging, (B)MRI/PET, (C) CT/PET, and (D) CT/SPECT.

NP as a disease cure

Nanoparticles have been shown to increase the rate of fibrillation of amyloidogenicproteins using assays based on the binding of thioflavin-T to protein fibrils39. Thepresence of 70 nm and 200 nm polymeric particles results in a reduced fibrillation time forâ-2-microglobulin (B2m), the protein involved in dialysisrelated amyloidosis. Thioflavin-Tassays in the absence (black) and presence of nanoparticles of different size andcomposition. As the thioflavin-T only fluoresces when it is bound to fibrils, the onset offluorescence correlates with the onset of fibrillation. TEM of the protein fibrils in thepresence of nanoparticles showing that the fibrils do not grow out from the nanoparticles.Scale bar: 100 nm.

Cytotoxicity of NPs on the plants

High resolution-microscopic images of roots of Phaseolus radiatus exposed toAgNPs: (A) control (25×), (B) root cell epidermis, control (400×), (C) root cellcortex, control (1000×), (D) 40 mg L−1 (25×), (E) root cell epidermis, 40 mg L−1

(400×), and (F) root cell cortex, 40 mg L−1 (1000×).

The NP in human body

Biodistribution of nanoparticles with varying coatings and bound proteins.Uncoated particles bind proteins and are taken up by the RES into the liver andspleen. “PEGylated” particles bind very few proteins, avoid uptake by the RES,and are longer circulating in the blood. “Polysorbate-coated” particles canspecifically bind ApoE and selectively target to the brain across the blood brainbarrier.