Doxorubicin Loaded Thermosensitive Magneto-Liposomes Obtained by a Gel Hydration Technique: Characterization and In Vitro Magneto-Chemotherapeutic Effect Assessment.

The combination of magnetic hyperthermia with chemotherapy is considered a promising strategy in cancer therapy due to the synergy between the high temperatures and the chemotherapeutic effects, which can be further developed for targeted and remote-controlled drug release. In this paper we report a simple, rapid, and reproducible method for the preparation of thermosensitive magnetoliposomes (TsMLs) loaded with doxorubicin (DOX), consisting of a lipidic gel formation from a previously obtained water-in-oil microemulsion with fine aqueous droplets containing magnetic nanoparticles (MNPs) dispersed in an organic solution of thermosensitive lipids (transition temperature of ~43 °C), followed by the gel hydration with an aqueous solution of DOX. The obtained thermosensitive magnetoliposomes (TsMLs) were around 300 nm in diameter and exhibited 40% DOX incorporation efficiency. The most suitable MNPs to incorporate into the liposomal aqueous lumen were Zn ferrites, with a very low coercive field at 300 K (7 kA/m) close to the superparamagnetic regime, exhibiting a maximum absorption rate (SAR) of 1130 W/gFe when dispersed in water and 635 W/gFe when confined inside TsMLs. No toxicity of Zn ferrite MNPs or of TsMLs was noticed against the A459 cancer cell line after 48 h incubation over the tested concentration range. The passive release of DOX from the TsMLs after 48h incubation induced a toxicity starting with a dosage level of 62.5 ug/cm2. Below this threshold, the subsequent exposure to an alternating magnetic field (20-30 kA/m, 355 kHz) for 30 min drastically reduced the viability of the A459 cells due to the release of incorporated DOX. Our results strongly suggest that TsMLs represent a viable strategy for anticancer therapies using the magnetic field-controlled release of DOX.

Enhanced Magnetic Hyperthermia Performance of Zinc Ferrite Nanoparticles under a Parallel and a Transverse Bias DC Magnetic Field.

The collective organization of magnetic nanoparticles (MNPs) influences significantly their hyperthermic properties, relevant for their in vitro and in vivo applications. We report a systematic investigation of the effects of the concentration and the static bias direct current (DC) magnetic field superposed over the alternating magnetic field (AMF), both in a parallel and perpendicular configuration, on the specific absorption rate (SAR) by using zinc ferrite MNPs. The nonmonotonic dependence of the SAR on the concentration, with a maximum at very small concentrations (c ≤ 0.1 mgFe/mL), followed by a minimum at 0.25 mgFe/mL, and the second maximum of 3.3 kW/gFe at around 1 mgFe/mL, was explained by the passage of the MNPs from a single particle behavior to a collective one and the role of the dipolar interactions. By superposing a static 10 kA/m bias DC field on the AMF we obtained an increase in the SAR for both parallel and perpendicular orientations, up to 4285 W/gFe and 4070 W/gFe, respectively. To the best of our knowledge, this is the first experimental proof of a significant enhancement of the SAR produced by a perpendicular DC field. The effect of the DC field to increase the SAR is accompanied by an increase in the hyperthermia coercive field (HcHyp) for both configurations. No enhancement of the DC fields was noticed for the MNPs immobilized in a solid matrix but the DC field increases the HcHyp only in the parallel configuration. This translates into a higher SAR value for the perpendicular configuration as compared to the parallel configuration. These results have practical applications for magnetic hyperthermia.

A Fast, Reliable Oil-In-Water Microemulsion Procedure for Silica Coating of Ferromagnetic Zn Ferrite Nanoparticles Capable of Inducing Cancer Cell Death In Vitro.

The applications of ferrimagnetic nanoparticles (F-MNPs) in magnetic hyperthermia (MH) are restricted by their stabilization in microscale aggregates due to magnetostatic interactions significantly reducing their heating performances. Coating the F-MNPs in a silica layer is expected to significantly reduce the magnetostatic interactions, thereby increasing their heating ability. A new fast, facile, and eco-friendly oil-in-water microemulsion-based method was used for coating Zn0.4Fe2.6O4 F-MNPs in a silica layer within 30 min by using ultrasounds. The silica-coated clusters were characterized by various physicochemical techniques and MH, while cytotoxicity studies, cellular uptake determination, and in vitro MH experiments were performed on normal and malignant cell lines. The average hydrodynamic diameter of silica-coated clusters was approximately 145 nm, displaying a high heating performance (up to 2600 W/gFe). Biocompatibility up to 250 µg/cm2 (0.8 mg/mL) was recorded by Alamar Blue and Neutral Red assays. The silica-coating increases the cellular uptake of Zn0.4Fe2.6O4 clusters up to three times and significantly improves their intracellular MH performances. A 90% drop in cellular viability was recorded after 30 min of MH treatment (20 kA/m, 355 kHz) for a dosage level of 62.5 µg/cm2 (0.2 mg/mL), while normal cells were more resilient to MH treatment.

Silica Coating of Ferromagnetic Iron Oxide Magnetic Nanoparticles Significantly Enhances Their Hyperthermia Performances for Efficiently Inducing Cancer Cells Death In Vitro.

Increasing the biocompatibility, cellular uptake, and magnetic heating performance of ferromagnetic iron-oxide magnetic nanoparticles (F-MNPs) is clearly required to efficiently induce apoptosis of cancer cells by magnetic hyperthermia (MH). Thus, F-MNPs were coated with silica layers of different thicknesses via a reverse microemulsion method, and their morphological, structural, and magnetic properties were evaluated by multiple techniques. The presence of a SiO2 layer significantly increased the colloidal stability of F-MNPs, which also enhanced their heating performance in water with almost 1000 W/gFe as compared to bare F-MNPs. The silica-coated F-MNPs exhibited biocompatibility of up to 250 µg/cm2 as assessed by Alamar Blues and Neutral Red assays on two cancer cell lines and one normal cell line. The cancer cells were found to internalize a higher quantity of silica-coated F-MNPs, in large endosomes, dispersed in the cytoplasm or inside lysosomes, and hence were more sensitive to in vitro MH treatment compared to the normal ones. Cellular death of more than 50% of the malignant cells was reached starting at a dose of 31.25 µg/cm2 and an amplitude of alternating magnetic field of 30 kA/m at 355 kHz.