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 γ-earboxylic acid of FA was successfully bound to the ligand of the Fe₃O₄ NPs without the loss of the a-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-Fe ₃O₄ 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.