Poly-sarcosine and Poly(Ethylene-Glycol) Interactions with Proteins Investigated Using Molecular Dynamics Simulations

Settanni, Giovanni; Schäfer, Timo; Muhl, Christian; Barz, Matthias; Schmid, Friederike

doi:10.1016/j.csbj.2018.10.012

Cited by 37 publications

(18 citation statements)

References 50 publications

(63 reference statements)

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“…Recent results demonstrate that PEG harvests specific apolipoproteins as a result of preferential binding, which inhibit uptake and elimination by the MPS. [79][80][81] The harvesting effect is observed in the tendency of F2 and F3 to attract more proteins per lipid to the surface and form thicker corona layers than F1. They show that while protein enrichment is modulated by surface coatings, accumulation of stealth-mediating apolipoproteins is not dependent on PEG.…”

Section: Stealth-mediating Proteins Enrich On Liposomes Regardless Ofmentioning

confidence: 99%

In situanalysis of liposome hard and soft protein corona structure and composition in a single label-free workflow

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Section: Stealth-mediating Proteins Enrich On Liposomes Regardless Ofmentioning

confidence: 99%

In situanalysis of liposome hard and soft protein corona structure and composition in a single label-free workflow

et al. 2020

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“…Recently, the interactions between PEG and individual amino acids have been quantified and applied to predict the extent of protein folding. Settanni et al simulated a mixture of PEG and plasma proteins such as serum albumin, transferrin, complement Cq1, and apolipoprotein A1, and calculated the local density of PEG near individual amino acids, the preferential binding coefficient of each peptide for PEG [59,60], and the conformation and thickness of PEG layer adsorbed on the protein surface [61], showing that PEG-protein interactions can be quantified by a simple model in terms of the solvent-accessible surface area exposed by each amino acid type on the protein surface, favorably compared with experimental results obtained by label-free proteomic mass spectrometry. Kurinomaru et al [62], Zaghmi et al [63], and Sindhu et al [64] found the effect of PEGylation on the structure, dynamics, and binding affinity of enzyme-therapeutic drugs such as α-amylase, glutamate dehydrogenase, and L-asparaginase, respectively.…”

Section: Proteinsmentioning

confidence: 99%

Molecular Simulations of PEGylated Biomolecules, Liposomes, and Nanoparticles for Drug Delivery Applications

Lee

2020

Pharmaceutics

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Since the first polyethylene glycol (PEG)ylated protein was approved by the FDA in 1990, PEGylation has been successfully applied to develop drug delivery systems through experiments, but these experimental results are not always easy to interpret at the atomic level because of the limited resolution of experimental techniques. To determine the optimal size, structure, and density of PEG for drug delivery, the structure and dynamics of PEGylated drug carriers need to be understood close to the atomic scale, as can be done using molecular dynamics simulations, assuming that these simulations can be validated by successful comparisons to experiments. Starting with the development of all-atom and coarse-grained PEG models in 1990s, PEGylated drug carriers have been widely simulated. In particular, recent advances in computer performance and simulation methodologies have allowed for molecular simulations of large complexes of PEGylated drug carriers interacting with other molecules such as anticancer drugs, plasma proteins, membranes, and receptors, which makes it possible to interpret experimental observations at a nearly atomistic resolution, as well as help in the rational design of drug delivery systems for applications in nanomedicine. Here, simulation studies on the following PEGylated drug topics will be reviewed: proteins and peptides, liposomes, and nanoparticles such as dendrimers and carbon nanotubes.

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“…As shell material we chose either i) poly(ethylene glycol) (PEG), [ 25,32 ] ii) poly( N ‐2‐hydroxypropylmethacrylamide) (pHPMA) [ 18,33,34 ] or iii) polysarcosine (pSar), [ 35,36 ] as they are not only considered protein resistant but furthermore are part of drugs in preclinical or clinical investigations. [ 21,37–39 ] Moreover, all these polymers are hydrophilic and do not possess a net charge to reduce adsorption of proteins by electrostatic and hydrophobic interactions. [ 40,41 ] In addition, it was recently demonstrated that the pSar based nanoparticles maintain their diffusion coefficient and thus hydrodynamic radius even in full human blood.…”

Section: Introductionmentioning

confidence: 99%

Polymeric Nanoparticles with Neglectable Protein Corona

Alberg

Krämer

Schinnerer

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with cells, [10] can shield recognition units, [15] but its role for biodistribution and circulation is still far from well understood. [8,16] Except for liposomes, other types of nano-sized drug delivery systems, such as polymeric micelles or more complex polymer constructs like cylindrical polymer brushes [17] have been so far hardly investigated with respect to protein corona formation (for comparison between the structures of these nanoparticles and the colloidal nanoparticles discussed above, see Figures S1 and S2 in the Supporting Information). [8,[18][19][20] However, the former are interesting, since polymeric micelles are in advanced stages of clinical testing (e.g., CPC634 (phase II) [21] and NC-6004 Nanoplatin (phase III) [22] ).To evaluate the formation of a protein corona, separation of the nanoparticle-protein-complex from unbound proteins used for incubation or upon in vivo exposure becomes a necessity. The isolation of incubated nanoparticles (colloids and inorganic nanoparticles) from unbound proteins was mainly performed by centrifugation, which is a separation method based on differences in density. [23] Thus, this method allows only the purification of nanoparticles with a higher density but can hardly be used for low density particles, such as polymeric micelles and polymer brushes. [24] Only recently, size exclusion techniques such as size exclusion chromatography and asymmetrical flow field-flow fractionation (AF4) have been employed for this purpose. [19,25,26] AF4 is a separation technique, which can be applied for the separation of particle and protein mixtures in the size range between 1 nm and 1 µm. [27,28] It consists of a separation channel with a flow gradient in which the particles are separated by an additional vertical force field depending on their diffusion coefficient. [29,30] During an AF4 measurement, the injected particles are pushed by the vertical cross flow toward the membrane at the bottom of the channel. Due to Brownian motion, the particles are diffusing back into the middle of the channel. Since smaller particles are faster than larger ones (because of their higher diffusion coefficient), they are concentrating faster in the middle, thus eluting first through the channel outlet. In contrast to conventional size exclusion chromatography, in AF4 the contact to the interface and the shear forces are substantially reduced, which leads to very mild separation conditions, minimizing perturbations of a potential protein corona. [26,31] Based on this method, Landfester and coworkers recently fully characterized the protein corona of Lutensol AT50-coated polystyrene nanoparticles and PEG functionalized liposomes, identifying all adsorbed proteins. [19,26] Here, we present a purification procedure based on AF4 for the separation of smaller polymeric architectures (R h : 20-30 nm) that are hardly separable by centrifugation. We isolated polymeric nanoparticles from unbound blood plasma components and characterized them by dynamic light scattering, gel electrophoresis and mass s...

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Poly-sarcosine and Poly(Ethylene-Glycol) Interactions with Proteins Investigated Using Molecular Dynamics Simulations

Cited by 37 publications

References 50 publications

In situanalysis of liposome hard and soft protein corona structure and composition in a single label-free workflow

In situanalysis of liposome hard and soft protein corona structure and composition in a single label-free workflow

Molecular Simulations of PEGylated Biomolecules, Liposomes, and Nanoparticles for Drug Delivery Applications

Polymeric Nanoparticles with Neglectable Protein Corona

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