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Abstract

In memory of Leone Spiccia Recently,w er eported ad etailed in vitro investigation of the "stealth"p roperties of USPIONs coated with a3 -(dimethylamino)propylamine derivativeo fp oly(maleic anhydride-alt-1decene) (PMAL), an amphiphilic zwitterionic polymer. [15,33] The PMAL-USPIONsp roveds uperior to USPIONs coated with octylamine-modifiedp olyacrylic acid, an egatively charged polymer, in terms of their ability to resist protein corona formation. [15] Encouraging resultsfrom that study,along with acontinued interest in developing NP-based multimodal imaging agents for in vivo use, have now led us to investigate the effect of zwitterionic modifications on the properties of polyacrylic-acid-coatedU SPIONs( PAA-USPIONs). Herein, we presentt he results of as tudy examiningt he serum protein adsorption characteristics, cellularu ptake and cytotoxicity of PAA-USPIONs functionalized with three low-molecular-weightc ompounds that impart zwitterionic character to the NP surface.G iven that previous studies have shown that the interactions of NPs with proteins and cells are nanomaterial-specifica nd dictate their ultimate metabolic fate, [10, 14, 16, 21-23, 27, 30, 34-38] examination of such Polyacrylic-acid-coated ultra-small super-paramagnetic iron oxide nanoparticles were surface-modified with low-molecularweights ulfobetaines or 3-(diethylamino)propylamine in order to generate nanoparticles with zwitterionic character (ZW-NPs).The ZW-NPs provedh ighly resistant to serum protein corona formationi nvitro, as revealed by atomic force microscopy, SDS-PAGE and proteomics analysis, and exhibited low cytotox-icity towardsA 431a nd HEK293c ells. The presence of unreacted carboxylic acid groups enableda dditional functionalization with fluorescent (Cy5) and radioactive [ 64 Cu-dmptacn; dmptacn = 1,4-bis(2-pyridinylmethyl)-1,4,7-triazacyclononane] moieties. Overall,t he ZW-NPs represent promising platforms for the development of new multimodald iagnostic/therapeutic agents possessing "stealth"properties.