Hyun Jin Lee, Kwang-Suk Jang, Hee-Man Yang, and Jong-Duk Kim*. Korea Advanced Institute of Science and Technology, Daejeon, South Korea
We report self-assmebled nanocarriers of poly(amino acid) derivatives loaded with superparamagnetic iron oxide (SPIO) nanoparticles for magnetic resonance imaging (MRI) and anticancer drug for chemotherapy. Hydrophobically modified synthetic poly(amino acid), poly(2-hydroxyethyl L-aspartamide) grafted with octadecyl chains (PHEA-g-C18) which self-assemble into spherical micellar aggregates in aqueous phase, was synthesized. For cancer-targeted system, cyclic RGD peptide was conjugated to the polymer system. Synthesis and molecular composition were confirmed with 1H-NMR and elemental analysis. SPIO nanoparticles well known as strong signal enhancer of T2-weighted MRI were synthesized with four different diameters, 4, 6, 8, and 10 nm, as previously reported by Sun et al. and characterized with XRD, TEM, SQUID magnetometer and FT-IR. The surface of nanoparticles is highly hydrophobidized with oleyl chains and the nanoparticles can be solubilized in nonpolar solvents. Solution of SPIO nanoparticles in mixture of chloroform/dimethylchloride was added into polymer solution in water and the mixture was vigorously vortexed to form microelusion. By remove of organic solvents and unloaded nanoparticles, stable micellar carriers loaded with SPIO nanoparticles were prepared. Physicochemical characteristics with variables of nanoparticle size and SPIO/Polymer ratio were studied by with DLS, TEM, ICP-AES and T2 mapping. Anticancer drug, doxorubicin (DOX), was successfully co-loaded by addition of DOX solution in THF into the carrier solution. Loading and in vitro release behavior of DOX was studied with UV/Vis spectroscopy. Since they show the great stability in aqueous phase and the high efficiency in enhancing MR contrast etc., their potential use as advanced delivery carriers is highly expected.