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Nanoparticle-corona study

Nanoparticle-corona study

What is the corona?Structural depictions of transferrin (TF) and the protein corona. Cartoon representation of the (chicken) TF polypeptidechain (protein database entry 1N04). Sketch showing a polymer-coated FePt nanoparticle covered by a monolayer of TF molecules.

Hard coronaThe term of hard corona defines the long-lived equilibrium state representing a fingerprint of a nanoparticle in a certain environmentNPprotein labeling strategies:electrostatic attachment of proteincovalent attachment to the NP ligandattachment of a protein cofactor on NPdirect linkage of amino acid on the NP core.

Several factors influence the corona composition Hydrophobicity

Size

Charge

Sequence

Topology

Reaction milieu

Hydrophobicity

SizeEffect 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

TopologyProtein 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 interactionsa) Structure of NP1 scaffold and the DNA backboneb) Transcription level as a function of DNANP1 stoichiometryc) Binding of DNA through complementary oligonucleotide hybridization.

equilibrium constantSchematic representation of the protein corona on a nanoparticle illustrating the exchange processes and equilibrium constants. The exchange rates are a complex function of the affinity for the surface, curvature effects from the surface, and changes in the surrounding milieu, and much work is needed to evaluate the equilibrium constants under different conditions.

What dose the cell see?Nanoparticleprotein complexes as seen by the cell. Immediately on contact with biological fluid, nanoparticles take on a corona of proteins (redyellow -helices and redblue -sheets) that exchange with their surroundings. Proteins that reside on the nanoparticle surface for much longer can be identified by cells. uptake of a nanoparticleprotein complex 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 protein for the receptor.

SeparationSize-exclusion chromatography study of nanoparticle-protein interactions. The elution time of proteins is shifted depending on their affinity for the nanoparticle surface, the longer the protein is associated with the nanoparticle the earlier the protein elutes from the column. Proteins that have sufficiently long residence times elute in the void volume with the nanoparticles. It is clear that each fraction collected from the size-exclusion column contains many different proteins, which can be further separated by gel electrophoresis using denaturing acrylamide gels as shown on the right. The different gel bands can be cut out and the proteins identified by mass spectrometry.

Dose the NP always unfold proteins?Schematic representation of artificial molecular chaperones

ApplicationsSchematic representation of nanoparticle-assisted multimodality 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 cureNanoparticles have been shown to increase the rate of fibrillation of amyloidogenic proteins using assays based on the binding of thioflavin-T to protein fibrils39. The presence of 70 nm and 200 nm polymeric particles results in a reduced fibrillation time for -2-microglobulin (B2m), the protein involved in dialysisrelated amyloidosis. Thioflavin-T assays in the absence (black) and presence of nanoparticles of different size and composition. As the thioflavin-T only fluoresces when it is bound to fibrils, the onset of fluorescence correlates with the onset of fibrillation. TEM of the protein fibrils in the presence 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 to AgNPs: (A) control (25), (B) root cell epidermis, control (400), (C) root cell cortex, control (1000), (D) 40mgL1 (25), (E) root cell epidermis, 40mgL1 (400), and (F) root cell cortex, 40mgL1 (1000).

The NP in human bodyBiodistribution of nanoparticles with varying coatings and bound proteins. Uncoated particles bind proteins and are taken up by the RES into the liver and spleen. PEGylated particles bind very few proteins, avoid uptake by the RES, and are longer circulating in the blood. Polysorbate-coated particles can specifically bind ApoE and selectively target to the brain across the blood brain barrier.

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