Search results for "stealth effect"
showing 7 items of 7 documents
Protein Corona: Prevention of Dominant IgG Adsorption on Nanocarriers in IgG‐Enriched Blood Plasma by Clusterin Precoating (Adv. Sci. 10/2019)
2019
The development of nanocarriers for drug delivery is challenged by individual blood composition fluctuations. In article number 1802199, Svenja Morsbach and co‐workers report the accumulation of immunoglobulins in the protein corona of nanocarriers in IgG‐enriched blood plasma resulting in increased cell uptake. This could be prevented by pre‐coating the nanocarriers with the “stealth” protein clusterin. Cover design by Stefan Schuhmacher.
Brush Conformation of Polyethylene Glycol Determines the Stealth Effect of Nanocarriers in the Low Protein Adsorption Regime
2021
For nanocarriers with low protein affinity, we show that the interaction of nanocarriers with cells is mainly affected by the density, the molecular weight, and the conformation of polyethylene glycol (PEG) chains bound to the nanocarrier surface. We achieve a reduction of nonspecific uptake of ovalbumin nanocarriers by dendritic cells using densely packed PEG chains with a "brush" conformation instead of the collapsed "mushroom" conformation. We also control to a minor extent the dysopsonin adsorption by tailoring the conformation of attached PEG on the nanocarriers. The brush conformation of PEG leads to a stealth behavior of the nanocarriers with inhibited uptake by phagocytic cells, whi…
Noncovalent Targeting of Nanocarriers to Immune Cells with Polyphosphoester‐Based Surfactants in Human Blood Plasma
2019
Abstract Dendritic cells (DCs) are part of the immune system and can internalize pathogens by carbohydrate receptors. The uptake induces maturation and migration of the DCs resulting in an adaptive immune response by presenting antigens to T‐cells. Thus, targeted delivery to DCs is a powerful tool for immunotherapy. However, in blood, specific targeting is challenging as blood proteins adsorb to the nanocarriers and mask the targeting molecules. Additionally, covalent coupling of targeting groups to nanocarriers requires new chemistry for each nanocarrier, while a general strategy is missing. A general protocol by noncovalent adsorption of mannosylated polyphosphoesters (PPEs) on the nanoca…
How Low Can You Go? Low Densities of Poly(ethylene glycol) Surfactants Attract Stealth Proteins.
2018
It is now well-established that the surface chemistry and “stealth” surface functionalities such as poly(ethylene glycol) (PEG) chains of nanocarriers play an important role to decrease unspecific protein adsorption of opsonizing proteins, to increase the enrichment of specific stealth proteins, and to prolong the circulation times of the nanocarriers. At the same time, PEG chains are used to provide colloidal stability for the nanoparticles. However, it is not clear how the chain length and density influence the unspecific and specific protein adsorption keeping at the same time the stability of the nanoparticles in a biological environment. Therefore, this study aims at characterizing the…
Poly(methyl ethylene phosphate) hydrogels
2020
Abstract A degradable and water-soluble polyphosphoester (PPE), namely poly(methyl ethylene phosphate)-dimethacrylate (PMEP-DMA), was synthesized and crosslinked by UV irradiation to prepare PPE-hydrogels. Hydrogels with 10 and 15 wt% of PMEP were prepared after UV-irradiation with an additional 0.2 wt% of photoinitiator. The colorless and transparent PPE hydrogels were studied for their swelling and water uptake. The rheological analysis demonstrated their viscoelastic behavior. The PPE hydrogels were compared to poly(ethylene glycol) (PEG) hydrogels prepared from PEG-macromonomers of similar degrees of polymerization. Hydrolysis experiments proved a successful disintegration of the PPE hy…
Polyphosphoester surfactants as general stealth coatings for polymeric nanocarriers
2020
Opsonization of nanocarriers is one of the most important biological barriers for controlled drug delivery. The typical way to prevent such unspecific protein adsorption and thus fast clearance by the immune system is the covalent modification of drug delivery vehicles with poly(ethylene glycol) (PEG), so-called PEGylation. Recently, polyphosphoesters (PPEs) were identified as adequate PEG substitutes, however with the benefits of controllable hydrophilicity, additional chemical functionality, or biodegradability. Here, we present a general strategy by non-covalent adsorption of different nonionic PPE-surfactants to nanocarriers with stealth properties. Polyphosphoester surfactants with dif…
Prevention of Dominant IgG Adsorption on Nanocarriers in IgG‐Enriched Blood Plasma by Clusterin Precoating
2019
Abstract Nanocarriers for medical applications must work reliably within organisms, independent of the individual differences in the blood proteome. Variation in the blood proteome, such as immunoglobulin levels, is a result of environmental, nutrition, and constitution conditions. This variation, however, should not influence the behavior of nanocarriers in biological media. The composition of the protein corona is investigated to understand the influence varying immunoglobulin levels in the blood plasma have on the interactions with nanocarriers. Specifically, the composition of the nanocarriers' coronas is analyzed after incubation in plasma with normal or elevated immunoglobulin G (IgG)…