Zwitterionic Modification of Ultra-Small Iron Oxide Nanoparticles for Reduced Protein Corona Formation

Polyacrylic acid-coated ultra-small super-paramagnetic iron oxide nanoparticles have been surface-modified with low-molecular weight sulfobetaines or N,N-diethylaminopropylamine 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 AFM, 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) moieties. Overall, the ZW-NPs represent promising platforms for the development of new multi-modal diagnostic/therapeutic agents possessing “stealth” properties.