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

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 cytotox-icity towards A431 and HEK293 cells. The presence of unreacted carboxylic acid groups enabled additional functionalization with fluorescent (Cy5) and radioactive [Cu-64-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.