Defined Coadsorption of Prostate Cancer Targeting Ligands and PEG on Gold Nanoparticles for Significantly Reduced Protein Adsorption in Cell Media

Abstract

A study on the surface chemistry of gold nanoparticles (AuNPs) utilizing gel electrophoresis is presented. The molecular design of targeting and stabilizing PEG ligands allows one to combine them in mixed ligand layers with control of relative composition. For all tested targeting and control ligands, coadsorption of PEG significantly reduces protein adsorption and matrix effects of cell media as compared to conjugates without PEG. Introducing carboxylic acid groups into the PEG ligand layer does not lead to increased protein adsorption as shown with carboxylic acid terminated PEG ligands. The controlled adsorption of PEG ligands with different molecular weights is used to disentangle the effects of particle charge and hydrodynamic diameter. Taken together, this study provides directions for the functionalization of nanoparticles to obtain conjugates which are well-defined in terms of composition and colloidally stable in complex media. This is in particular relevant for targeting applications and cell experiments.

Encapsulation of Nanoparticles with Statistical Copolymers with Different Surface Charges and Analysis of Their Interactions with Proteins and Cells

“…Notably, the ζ-potentials do not necessarily reflect the surface charge/potential of the conjugates but refer to the potential at the shearing plane when the particles are moved in an external electric field. In particular, for polymer coatings this means that measured ζ-potentials are not necessarily the ones we would expect based on the formal charge, as discussed recently [33].…”

“…Notably potentials do not necessarily reflect the surface charge/potential of the conjugates b to the potential at the shearing plane when the particles are moved in an external field. In particular, for polymer coatings this means that measured ζ-potentials necessarily the ones we would expect based on the formal charge, as discussed r [33]. In the case of plasmonic gold nanoparticles (Au NPs), aggregation leads to pla coupling, which drastically changes the optical properties [53].…”

“…This is a complex process that delicately depends on the physicochemical properties of both the material and the binding properties, as well as the composition of the medium/matrix. Two prominent strategies to reduce unwanted protein adsorption are PEGylation (the binding of poly(ethylene glycol) (PEG)-based ligands to nanomaterials) [3,[33][34][35][36][37] on the one hand and the use of small zwitterionic ligands on the other [38][39][40][41][42]. Even though these strategies seem to be very different, relying on uncharged polymers on the one hand or on small mixed-charged molecules on the other, they are both based on a strong hydration of the ligand shell for minimized protein binding [43,44].…”

Engineering a material-genetic interface as safety switch for embedded therapeutic cells

“…The most widely used among these is polyethylene-glycol (PEG), being FDA-approved since 1995 25 and having been used for several drug formulations since 26 . Due to its excellent biocompatibility and physicochemical properties (such as low protein adsorption, which results in less immunogenicity 27 ), PEG is highly compliant with the requirements for therapeutic cell encapsulation.…”

Composite ligand shells on gold nanoprisms – an ensemble and single particle study

“…[13][14][15][16] When not only a single type, but a combination of thiols is used, the surface modication gets even more complex, and can lead even to the formation of molecular patches. [17][18][19] It was found earlier, that when a mixture of thiolated PEG and small thiols is applied to gold nanoparticles on the time scale of hours, the small thiols can dominate the adsorbed layer during competitive adsorption. 20 This is consistent with results obtained when the thiolated PEG and the small thiol are applied consecutively, showing that small molecules can more effectively replace PEG on the hour time scale, but at the same time not only thiol exchange, but also backlling process can take place, that is the second thiol occupies still available binding sites at the particle surface resulting in a composite ligand layer.…”