Brush Conformation of Polyethylene Glycol Determines the Stealth Effect of Nanocarriers in the Low Protein Adsorption Regime

Mengyi Li,Johanna Simon,Katharina Landfester,Shuai Jiang,Volker Mailänder,Manfred Wagner,David Paßlick,Marie-Luise Frey,Daniel Crespy

doi:10.1021/acs.nanolett.0c03756

Abstract

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, which is a prerequisite for successful in vivo translation of nanomedicine to achieve long blood circulation and targeted delivery. We can clearly correlate the brush conformation of PEG with inhibited phagocytic uptake of the nanocarriers. This study shows that, in addition to the surface’s chemistry, the conformation of polymers controls cellular interactions of the nanocarriers.

Highlights

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
O nce nanoparticles enter the bloodstream, the adsorption of blood proteins on their surfaces usually leads to the formation of a protein corona, which switches their synthetic identity toward a biological identity depicted by bounded proteins
We have shown that modifying polymer nanoparticles with attached polyethylene glycol (PEG)[1] and alternative hydrophilic polymers, e.g., poly(phosphoester)[1,4] and polysaccharide,[5] leads to the enrichment of clusterin in protein corona, which was proved to be responsible for the stealth effect of the nanoparticles

Summary

PEG conformation

10.0 brush aThese parameters were used to predict the PEG conformation according to the model of de Gennes.[17]. We compared the abundance of serum albumin and clusterin on OVA-NCs modified with the same number of ethylene glycol units per nm[2] (Figure 2f) for which different PEG conformations were formed from varied Mw and density combinations. Varied thresholds regarding the Mw31 and surface density[7,11] of the PEG were reported for achieving an effective inhibition of protein adsorption and/or cellular uptake, which can be attributed to different material properties of nanoparticles and PEG quantification methods.[33] Walkey et al.[32] found that, in addition to reduced macrophage uptake, an increase in the PEG density changes the composition of the adsorbed protein layer and decreases the total serum protein adsorption.

■ REFERENCES

Findings

Nanoparticle Size and Surface Chemistry Determine Serum Protein