Surface Functionalization of Iron Oxide Nanoparticles With Polymers and Small Molecules: Synthesis, Characterization, and Evaluation of Magnetic Hyperthermia Performance

A systematic investigation of various surface coatings on iron oxide nanoparticles (IONPs) was conducted to understand their influence on interfacial interactions, colloidal stability, and magnetic performance. The surface-modified IONPs were synthesized via in situ and physical coating routes using synthetic polymers (polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), polyethene glycol (PEG), polyethylenimine (PEI)), natural polymers (chitosan (CS), carboxymethyl cellulose (CMC), hyaluronic acid (HA)), small molecules (citric acid (CA), and oleic acid (OA)), and a silane coupling agent (3-aminopropyltriethoxysilane (APTES)). Face-centred cubic spinel-structured magnetite (Fe₃O₄) nanoparticles were synthesized with a lattice parameter of 8.356 Å, a particle size of 62 nm, and a saturation magnetization (M_s) of 67.95 A m² kg^-1. The coating of IONPs was confirmed by X-ray Photoelectron Spectroscopy (XPS) and Fourier Transform Infrared (FTIR) spectroscopy, indicating the formation of coordination bonds, hydrogen bonds, and electrostatic interactions between the NPs and the polymeric shell. The coatings substantially reduced agglomeration, thereby decreasing the particle size to 19-30 nm, while maintaining nearly superparamagnetic behavior at room temperature. The magnetic behavior was governed by Néel relaxation for NPs with a size less than 25 nm, whereas larger particles exhibited Brownian relaxation dominance. The relaxation mechanism is responsible for the heating output, measured as the Specific absorption rate (SAR), which provides a useful metric for comparing the heating efficiency of NPs. Induction heating studies carried out under the alternating magnetic field strength of 12.89 kA m^-1 and frequency of 336 kHz revealed that coated IONPs exhibited superior heating performance with improved SAR of 112 to 225 W g^-1. PEG, CMC, PEI, and APTES-coated IONPs achieved the hyperthermia temperature range of 42-46°C. However, PEG, CMC, and PEI-coated IONPs exhibited Néel relaxation dominance, which is desirable for in vivo hyperthermia applications. Furthermore, all the coated IONPs (except PEI-IONPs) demonstrated excellent in vitro cytocompatibility (> 80%) with the human embryonic kidney (HEK293) cell line at 2 mg mL^-1 for 72 h. Simulated hyperthermic conditions led to cancer cell lethality, with normal cells being largely viable, suggesting the efficacy of hyperthermia for cancer treatment.