Tuning the Surface of Nanoparticles: Impact of Poly(2‐ethyl‐2‐oxazoline) on Protein Adsorption in Serum and Cellular Uptake

Abstract

Due to the adsorption of biomolecules, the control of the biodistribution of nanoparticles is still one of the major challenges of nanomedicine. Poly(2-ethyl-2-oxazoline) (PEtOx) for surface modification of nanoparticles is applied and both protein adsorption and cellular uptake of PEtOxylated nanoparticles versus nanoparticles coated with poly(ethylene glycol) (PEG) and non-coated positively and negatively charged nanoparticles are compared. Therefore, fluorescent poly(organosiloxane) nanoparticles of 15 nm radius are synthesized, which are used as a scaffold for surface modification in a grafting onto approach. With multi-angle dynamic light scattering, asymmetrical flow field-flow fractionation, gel electrophoresis, and liquid chromatography-mass spectrometry, it is demonstrated that protein adsorption on PEtOxylated nanoparticles is extremely low, similar as on PEGylated nanoparticles. Moreover, quantitative microscopy reveals that PEtOxylation significantly reduces the non-specific cellular uptake, particularly by macrophage-like cells. Collectively, studies demonstrate that PEtOx is a very effective alternative to PEG for stealth modification of the surface of nanoparticles.

Poly(2‐oxazoline) Hydrogels: State‐of‐the‐Art and Emerging Applications

“…Although this group did not perform circulation studies they did investigate their nanogels for induced hemolysis and erythrocyte aggregation and found no significant interaction of the nanogels with blood. Other recent studies on PEtOx modified nanoparticles and PMeOx coated viruses, each without the ability to vary the zeta potential, similarly found reduced interaction of PAOx modified materials with cells.…”

Controlling nanoemulsion surface chemistry with poly(2-oxazoline) amphiphiles

“…68,69 Recent work has suggested that poly(2-methyl-2-oxazoline) has similar protein repellent features to poly(ethylene oxide). [70][71][72] Poly(2-oxazoline)s (POx) are synthesized through a controlled, living polymerization, facilitating tunable block structure, length, and selective comonomer addition. 73,74 Based on these collective attributes, we focused on amphiphilic poly(2-oxazoline) surfactants to decouple the physiochemical properties of nanoemulsions and facilely control their surface chemistry.…”

Possibilities and Limitations of Different Separation Techniques for the Analysis of the Protein Corona

“…[39][40][41] As highlighted by Maskos and co-workers even absolute particle sizes can be calculated from the retention times by calibrating the system with standard-size particles. [42] However,u pt ov ery recently AF4 was not commonly adopted to separate free proteins from nanocarrier-protein complexes for further corona analysis.In summary,the above-mentioned works have exploited AF4 as an analytical method to evaluate the change of retention time due to size increase,b ut not as as eparation tool for further protein corona analysis with ex situ measurements.…”