Polymer-Grafted, Nonfouling, Magnetic Nanoparticles Designed to Selectively Store and Release Molecules via Ionic Interactions

Surface functionalization of superparamagnetic iron oxide nanoparticles (IONPs) was achieved by exploiting a grafting "onto" approach simultaneously with an in situ modification of the graft block copolymer. Terminal phosphonic-acid-bearing block copolymers composed of pendant-activated ester moieties, that is, poly(pentafluorophenyl acrylate) (P(PFPA)) and poly(oligoethylene glycol acrylate) (P(OEGA)), were synthesized and assembled on IONP surfaces. The assembly was performed in the presence of different primary amines to introduce different functionality to the grafted chains, followed by subsequent thiol-ene Michael additions with acrylates or maleimides to decorate the IONP surface. The aim of this "double"-click chemistry on the polymer-coated nanoparticles was to generate a library of IONPs consisting of an internal layer of functionalized polyacrylamides and an outer shell of antifouling P(OEGA) decorated with fluorescent ligands. The resultant multifunctionalized IONPs were characterized using ATR-FTIR, XPS and TGA, proving the presence of modified polymers on the IONP surfaces. The functionalized nanoparticles proved to be stable in both water and phosphate buffer containing bovine serum albumin. Zeta potentials of the functionalized nanoparticles could be tuned by the judicious choice of functional groups introduced by the primary amines, for example, spermine, 3-(dimethylamino)-1-propylamine, L-lysine, L-histidine, L-arginine, beta-alanine, and taurine. Depending on the pH of IONP dispersions, the charge induced by functional groups within the polymer shell was used to encapsulate ionic dyes (methyl blue and rhodamine 6G in cationic and anionic layers, respectively), serving as models for drug loading via ionic complexation. The attachment of fluorophore through thiol-ene Michael addition was demonstrated by conjugating fluorescein-O-acrylate, as monitored by fluorescence spectroscopy. Cytotoxicity studies revealed that multifunctionalized IONPs were nontoxic to normal human lung fibroblast cell lines. Fluorescence lifetime imaging microscopy was employed to demonstrate the complexation and release of rhodamine 6G dye from L-lysine-functionalized IONPs.