Chemoselective Synthesis of Folic Acid-Functionalized Magnetite Nanoparticles via Click Chemistry for Magnetic Hyperthermia

Folic acid-functionalized Fe3O4 nanoparticles (FA-Fe3O4 NPs) were synthesized from iron(III) 3-allylacetylacetonate (IAA) through in situ hydrolysis and ligand modification, by applying the principle of "click chemistry". The gamma-carboxylic acid of FA was successfully bound to the ligand of the Fe3O4 NPs without the loss of the alpha-carboxylic acid group of folic acid (FA), which has an affinity for folate receptors (FRs) expressed on tumor cells. The Fe3O4 NPs were monodisperse, and their size was controlled by varying the conditions of IAA hydrolysis. The FA-Fe3O4 NPs, which had diameters of 8 nm, exhibited superparamagnetic behavior and a relatively high magnetization at room temperature. The blocking temperature was determined to be 220 K, and the magnetization curve exhibited a remanence of 19 emu/g and a coercivity of 550 Oe at 5 K. The specific absorption rate (SAR) was dependent on the size of the FA-Fe3O4 NPs and the strength of the applied magnetic field. The SAR of the 8-nm FA-Fe3O4 NPs was 670 W/g in a 230 kHz alternating magnetic field and 100 Oe. The chemoselective surface modification of magnetite particles with FA yielded a novel cancer-targeting system for use in hyperthermia treatment.