Fe3O4-PAA-(HP-γ-CDs) Biocompatible Ferrimagnetic Nanoparticles for Increasing the Efficacy in Superparamagnetic Hyperthermia.

ABSTRACT

In this paper, we present the obtaining of Fe3O4-PAA-(HP-γ-CDs) ferrimagnetic nanobioconjugates (PAA polyacrylic acid, HP-γ-CDs hydroxypropyl gamma-cyclodextrins) in a hybrid core-shell biostructure (core inorganic Fe3O4 nanoparticles, and shell organic PAA-(HP-γ-CDs)) and their use in superparamagnetic hyperthermia without cellular toxicity and with increased efficacy for future alternative cancer therapy. In order to design the optimal experimental conditions for obtaining nanobioconjugates and then superparamagnetic hyperthermia (SPMHT), we used molecular docking simulation and computational assessment of the maximum specific loss power (SLP) that led to nanoparticles' heating. The nanoparticles and nanobioconjugates obtained were studied and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transformed-infrared spectroscopy (FT-IR), dynamic light scattering (DLS), and magnetic measurements (MMs). The cell viability of the nanoparticles and nanobioconjugates was assessed by means of the MTT assay using human immortalized keratinocytes (HaCaT) as an in vitro model. Superparamagnetic hyperthermia with nanoparticles and nanobioconjugates was obtained experimentally in a magnetic field of 15.92 kA/m and frequency of 312.2 kHz for the magnetic nanoparticle core with a (average) diameter of 15.8 nm, which resulted in the maximum hyperthermic effect that led to a temperature of ~42.5 °C necessary in the therapy of tumors in a short time so as not to affect healthy tissues. The biological screening of Fe3O4-PAA nanoparticles and PAA-(HP-γ-CDs) nanobioconjugates showed no cytotoxic effect on HaCaT cells for a time interval of 24 h, both under standard (37 °C) and hyperthermia conditions (42.5 °C). Thus, Fe3O4-PA-(HP-γ-CDs) ferrimagnetic nanobioconjugates can be used successfully in superparamagnetic hyperthermia without toxicity and with increased efficiency due to the small layer thickness of the PAA-(HP-γ-CDs) shell, which is suitable in this alternative therapeutic technique.