Zwitterionic Modification of Ultrasmall Iron Oxide Nanoparticles for Reduced Protein Corona Formation

Abstract

Polyacrylic‐acid‐coated ultra‐small super‐paramagnetic iron oxide nanoparticles were surface‐modified with low‐molecular‐weight sulfobetaines or 3‐(diethylamino)propylamine in order to generate nanoparticles with zwitterionic character (ZW‐NPs). The ZW‐NPs proved highly resistant to serum protein corona formation in vitro, as revealed by atomic force microscopy, SDS‐PAGE and proteomics analysis, and exhibited low cytotoxicity towards A431 and HEK293 cells. The presence of unreacted carboxylic acid groups enabled additional functionalization with fluorescent (Cy5) and radioactive [64Cu–dmptacn; dmptacn=1,4‐bis(2‐pyridinylmethyl)‐1,4,7‐triazacyclononane] moieties. Overall, the ZW‐NPs represent promising platforms for the development of new multimodal diagnostic/therapeutic agents possessing “stealth” properties.

Label-free plasmonic nanostar probes to illuminate in vitro membrane receptor recognition

“…Typically, BSA or high density layers of polyethyleneglycol (PEG) are grafted to NPs to inhibit protein adsorption 11. However, there has been a number of recent studies that have reported that functionalizing a zwitterionic surface to the NP surface will reduce the formation of the protein corona 13,14,44. Therefore, it is not unusual that the RGDFC peptide, which has both a positive (arginine) and negative (glutamic acid) residue, exhibits reduced formation of the hard protein corona.…”

Theranostic Approach for the Protein Corona of Polysaccharide Nanoparticles

“…Taking into account the fact that the PC is formed anyway, it offers a therapeutic direction in two ways: i) a restriction of the PC formation to maintain the original functionality of NPs. In this case, coating by polymers (PEG, polyoxyethylene, poloxamine, zwitterions [64] or polysaccharides such as CS [65,66] ) could be employed. CS is an important natural proton sponge material that facilitates endosomal escape.…”

Biohybrid Nanoparticles to Negotiate with Biological Barriers

“…To possess antifouling properties, materials surface must possess charge neutrality in the scale comparable to proteins size, i.e., angstrom‐to‐nanoscale . Phosphatidylcholine, sulfobetaines, carboxybetaine, cysteine are such functional groups, endowing NPs with a zwitterionic surface chemistry. It is noteworthy that polyzwitterions are a class of materials, where alternative cations and anions have conformed a homogenous charge distribution in nanoscale, mimicking the innate charge conformation of proteins.…”