Multidentate Catechol-Based Polyethylene Glycol Oligomers Provide Enhanced Stability and Biocompatibility to Iron Oxide Nanoparticles

Abstract

We have designed, prepared, and tested a new set of multidentate catechol- and polyethylene glycol (PEG)-derivatized oligomers, OligoPEG-Dopa, as ligands that exhibit strong affinity to iron oxide nanocrystals. The ligands consist of a short poly(acrylic acid) backbone laterally appended with several catechol anchoring groups and several terminally functionalized PEG moieties to promote affinity to aqueous media and to allow further coupling to target molecules (bio and others). These multicoordinating PEGylated oligomers were prepared using a relatively simple chemical strategy based on N,N'-dicyclohexylcarbodiimide (DCC) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) condensation. The ability of these catechol-functionalized oligomers to impart long-term colloidal stability to the nanoparticles is compared to other control ligands, namely, oligomers presenting several carboxyl groups and monodentate ligands presenting either one catechol or one carboxyl group. We found that the OligoPEG-Dopa ligands provide rapid ligand exchange, and the resulting nanoparticles exhibit greatly enhanced colloidal stability over a broad pH range and in the presence of excess electrolytes; stability is notably improved compared to non-catechol presenting molecular or oligomer ligands. By inserting controllable fractions of azide-terminated PEG moieties, the nanoparticles (NPs) become reactive to complementary functionalities via azide-alkyne cycloaddition (Click), which opens up the possibility of biological targeting of such stable NPs. In particular, we tested the Click coupling of azide-functionalized nanoparticles to an alkyne-modified dye. We also measured the MRI T(2) contrast of the OligoPEG-capped Fe(3)O(4) nanoparticles and applied MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay to test the potential cytotoxicity of these NPs to live cells; we found no measurable toxicity to live cells.