Single and Dual Surfactants Coated Hydrophilic Superparamagnetic Iron Oxide Nanoparticles for Magnetic Fluid Hyperthermia Applications.

Superparamagnetic iron oxide nanoparticles (SPIONs) have found applications in the magnetic fluid hyperthermia (MFH) due to their unique magnetic properties, chemical stability and biocompatibility. However, challenges exist in attaining high heating efficiencies of the SPIONs under the applied alternating magnetic fields below Hergt's biological safety limit. Here, we present synthesis of single surfactant (pyromellitic acid (PMA)/2-aminoterephthalic acid (ATA)) and dual surfactants (PMA-ATA) coated SPIONs via chemical co-precipitation method and characterization to determine their phase purity, surface coatings and particle sizes. The hydrodynamic sizes/zeta potentials values of the SPIONs were determined for studying their water-dispersibility. Finally, the impact of heating on specific absorption rate (SAR) and intrinsic loss of power (ILP) were determined. SPIONs were found to exhibit magnetite phase and particle sizes in the range of 9-10 nm, good water dispersibility with (i) hydrodynamic diameters ranging from 190-304 nm and (ii) zeta potentials ranging from -38 mV to -49 mV. The ATA and PMA-ATA coated SPIONs showed better time-dependent temperature rise that resulted in higher heating efficacies-i.e., SAR and ILP values ranging from 58.6-79.5 W/gFe and 1.7-2.3 nHm²/Kg, respectively as compared to the PMA coated SPIONs. Thus, ATA and PMA-ATA coated SPIONs were found to be very promising candidates for their usage in MFH applications.

Functionalized Hydrophilic Superparamagnetic Iron Oxide Nanoparticles for Magnetic Fluid Hyperthermia Application in Liver Cancer Treatment.

In this work, we report the synthesis of hydrophilic and surface-functionalized superparamagnetic iron oxide nanoparticles (SPIOs) to utilize them as nanomedicines for treating liver cancer via magnetic fluid hyperthermia (MFH)-based thermotherapy. For this purpose, initially, we have synthesized the SPIOs through co-precipitation/thermolysis methods, followed by in situ surface functionalization with short-chained molecules, such as 1,4-diaminobenzene (14DAB), 4-aminobenzoic acid (4ABA) and 3,4-diaminobenzoic acid (34DABA) and their combination with terephthalic acid (TA)/2-aminoterephthalic acid (ATA)/trimesic acid (TMA)/pyromellitic acid (PMA) molecules. The as-prepared SPIOs are investigated for their structure, morphology, water dispersibility, and magnetic properties. The heating efficacies of the SPIOs are studied in calorimetric MFH (C-MFH) with respect to their concentrations, surface coatings, dispersion medium, and applied alternating magnetic fields (AMFs). Although all of the as-prepared SPIOs have exhibited superparamagnetic behavior, only 14DAB-, 4ABA-, 34DABA-, and 4ABA-TA-coated SPIOs have shown higher magnetization values (Ms = 55-71 emu g-1) and good water dispersibility. In C-MFH studies, 34DABA-coated SPIO-based aqueous ferrofluid (AFF) has revealed faster thermal response to the applied AMF and reached therapeutic temperature even at the lowest concentration (0.5 mg mL-1) compared with 14DAB-, 4ABA-, and 4ABA-TA-coated SPIO-based AFFs. Moreover, 34DABA-coated SPIO-based AFF has exhibited high heating efficacies (i.e., specific absorption rate/intrinsic loss power values of 432.1 W gFe-1/5.2 nHm2 kg-1 at 0.5 mg mL-1), which could be mainly due to (i) enhanced π-π conjugation paths of surface-attached 34DABA coating molecules because of intrafunctional group attractions and (ii) improved anisotropy from the formation of clusters/linear chains of the SPIOs in ferrofluid suspensions, owing to interfunctional group attractions/interparticle interactions. Moreover, the 34DABA-coated SPIOs have demonstrated (i) very good cytocompatibility for 24/48 h incubation periods and (ii) higher killing efficiency of 61-88% (via MFH) in HepG2 liver cancer cells as compared to their treatment with only AMF/water-bath-based thermotherapy. In summary, the 34DABA-coated SPIOs are very promising heat-inducing agents for MFH-based thermotherapy and thus could be used as effective nanomedicines for cancer treatments.

Systematic magnetic fluid hyperthermia studies of carboxyl functionalized hydrophilic superparamagnetic iron oxide nanoparticles based ferrofluids.

We have systematically studied heating efficiencies (via specific absorption rate-SAR/intrinsic loss power-ILP) of carboxyl (terephthalic acid-TA) functionalized hydrophilic SPIONs based ferrofluids (with good biocompatibility/high magnetization) and influence of following key factors in magnetic fluid hyperthermia (MFH): (i) alternating magnetic fields (AMFs - H)/frequencies (f) - chosen below/above Hergt's biological safety limit, (ii) concentrations (0.5-8 mg/ml) and (iii) dispersion media (water, a cell-culture medium and triethylene glycol (TEG)) for in vitro cancer therapy. In calorimetric MFH, aqueous ferrofluids have displayed excellent time-dependent temperature rise for the applied AMFs, which resulted in high SAR ranging from 23.4 to 160.7 W/gFe, attributed to the enhanced magnetic responses via π-conjugations of short-chained TA molecules on the surface of SPIONs. Moreover, ILP values up-to 2.5 nHm2/kg (higher than the best commercial ferrofluids) are attained for the aqueous ferrofluids when excited below the recommended safety limit. Besides, the SPIONs dispersed in high viscous TEG have exhibited the highest SAR value (178.8 W/gFe) and reached therapeutic temperatures at faster rates for the lowest concentration due to prominent Neel relaxations. Moreover, these SPIONs have higher killing efficiency towards MCF-7 cancer cells in in vitro studies. Thus, the TA-based ferrofluids have great potential for in vivo/clinical MFH cancer therapies.