Magnetic nanorods for remote disruption of lipid membranes by non-heating low frequency magnetic field.

This work presents direct evidence of disordering of liposomal membranes by magnetic nanoparticles during their exposures to non-heating alternating Extremely Low Frequency Magnetic Field (ELF MF). Changes in the lipid membrane structure were demonstrated by the Attenuated total reflection Fourier Transform Infrared and fluorescence spectroscopy. Specifically, about 50% of hydrophobic chains became highly mobile under the action of ELF MF. Magnetic field-induced increase in the membrane fluidity was accompanied by an increase in membrane permeability and release of solutes entrapped in liposomes. The effect of ELF MF on the membrane fluidity was greater in case of 70 × 12 nm magnetite nanorods adsorbed on the liposomes surface compared to liposomes with ~7 nm spherical MNPs embedded within lipid membranes. A physical model of this process explaining experimental data is suggested. The obtained results open new horizons for the development of systems for triggered drug release without dangerous heating and overheating of tissues.

Microencapsulated Multicellular Tumor Spheroids as a Tool to Test Novel Anticancer Nanosized Drug Delivery Systems In Vitro.

In the study, MCF-7 human breast adenocarcinoma cells were used to study cytotoxicity of novel anticancer nanosized formulations, such as docetaxel-loaded nanoemulsion and liposomal formulation of a lipophilic methotrexate (MTX) prodrug. In vitro study of cytotoxicity was carried out in 2 models, namely using 3D in vitro model based on multicellular tumor spheroids (MTS) and 2D monolayer culture. MTS were generated by tumor cell cultivation within alginate-oligochitosan microcapsules. In the case of the monolayer culture, cell viability was found to be 25, 18 and 12% for the samples containing nanoemulsion at concentrations 20, 300 and 1000 nM of docetaxel, respectively, after 48 hs incubation. For MTS these values were higher, namely 33, 23 and 18%, respectively. Cytotoxicity of liposomal MTX prodrug-based formulation with final concentration of 1, 2, 10, 50, 100 and 1000 nM in both models was also studied. MTX liposomal formulation demonstrated lower cytotoxicity on MTS compared to intact MTX. Moreover, MTS were also more resistant to both liposomal formulation and intact MTX than the monolayer culture. Thus, at 1000 nM MTX in the liposomal form, cell viability in MTS was 1.4-fold higher than that in the monolayer culture. MTS could be proposed as a promising tool to test novel anticancer nanosized formulations in vitro.