Application of biocompatible and ultrastable superparamagnetic iron(III) oxide nanoparticles doped with magnesium for efficient magnetic fluid hyperthermia in lung cancer cells.

ABSTRACT

Magnetic fluid hyperthermia (MFH) is a promising therapeutic strategy that targets malignant tissues by heating to 40-43 °C using magnetic nanoparticles (MNPs) subjected to an alternating magnetic field (AMF). In this study, novel magnetic iron(III) oxide nanoparticles doped with magnesium (Mg0.1-γ-Fe2O3(mPEG-silane)0.5) were synthesized, and their structural, chemical, and magnetic properties were analyzed using the following techniques Fourier-transform infrared spectroscopy, Raman spectroscopy, vibrating magnetometer analysis, powder X-ray diffraction, inductively coupled plasma mass spectrometry, scanning electron microscopy, high-resolution transmission electron microscopy, and energy-dispersive X-ray spectroscopy. The as-synthesized MNPs were used as water ferrofluids for MFH under an AMF in two calorimetric setups, namely phantom and lung cancer cell (A549) models. The as-synthesized MNPs were hexagonal or rhombohedral shaped, with an average size of 27 nm. They showed a typical soft ferromagnetic behavior based on the hysteresis profile, with a magnetic saturation of 70 emu g-1 and remnant magnetization of 1.6 emu g-1. In phantom studies, the ferrofluid (3.0 mg mL-1) exposed to an AMF (18.3 kA m-1, 110.1 kHz) heated up extremely quickly, reaching more than 90 °C in the first 10 min of magnetization. In cell studies, the ferrofluid (0.25 mg mL-1) under an AMF (16.7 kA m-1, 110.1 kHz) showed a slight increase in temperature within the first 12 min, reaching a peak of ca. 43-45 °C, which was stable up to the end of the AMF exposure (45 min). Under these conditions, a pronounced cytotoxic effect on the lung cancer cells was observed (viability ca. 15-20%). No such deleterious effects were observed when the cells were treated with MNPs only without an AMF. Specific absorption rate (SAR) measurements were performed using three mathematical approaches, namely the initial slope method, the corrected slope method, and the Box-Lucas method, which ranged from ca. 429 to 596 W g-1 for phantom and cell studies. Iron(III) oxide MNPs doped with magnesium were found to be candidates for MFH in lung cancer treatments.