Magnetically sensitive nanocomposites and magnetic liquids based on magnetite, gemcitabine, and antibody HER2
The processes of adsorption of gemcitabine (GC) on the surface of nanosized singledomain magnetite (Fe<sub>3</sub>O<sub>4</sub>) have been investigated. Under the experiment conditions, the value of adsorption capacity A was ~ 37.2 mg/g, the extraction extent U = 33.13 %, the separation factor E = 82.58 mL/g. It has been determined that adsorption corresponds to the Freundlich model. The magnetic properties of nanocomposites (NС) Fe<sub>3</sub>O<sub>4</sub>@GC have been investigated. The average value of the thickness of the adsorbed layer of GC in the composition of Fe<sub>3</sub>O<sub>4</sub>@GC NC is 2.4±0.1 nm, as evaluated by the method of magnetic granulometry. Magnetic liquids (ML) have been synthesized based on magnetite and physiological solution (PS) stabilized with sodium oleate (Ol.Na) and polyethylene glycol (PEG), which contain GC and antibody (AB) HER2 (Fe<sub>3</sub>O<sub>4</sub>@GC/Ol.Na/PEG+PS). The properties of ML were investigated as well as cytotoxic/cytostatic activity with respect to HepG2 hepatocellular carcinoma of human liver. Parameters of ML based on magnetite were found: Fe<sub>3</sub>O<sub>4</sub> concentration - 14 mg/mL, Fe<sub>3</sub>O<sub>4</sub> particle size - 4-22 nm, average size of Fe<sub>3</sub>O<sub>4</sub> particles - 10.8 nm; the average size of Fe<sub>3</sub>O<sub>4</sub> particles stabilized with sodium oleate - 16.8 nm, saturation magnetization M∞ = 14.1±2.5 % Gs, hypsometric height - 25±10 % cm, viscosity η = 1.14±3 % mPa∙s, density ρML = 1.14 ± 1.0 % g/cm <sup> 3 </sup> , the concentration of GC was 1.25 mg/mL, that of HER2 AB was 3.75 μg/mL. We have obtained the calculated and graphic data concerning the dependence of the surface area and the specific magnetization of saturation of Fe<sub>3</sub>O<sub>4</sub>@GC/Ol.Na/PEG on the thickness of GC layer, which can be useful for predicting of the nanoscale architecture of magnetically sensitive NC and ML in the manufacture of relative drugs. The synergistic nature of the influence of GC/Fe<sub>3</sub>O<sub>4</sub>/HER2 complex on HepG2 cells was revealed. It has been determined that IC50 for ML is 0.155 mg/mL, in the range of concentration of 0.025-0.1 mg/mL, ML is biocompatible with HepG2 cells. It has been shown that HER2 AB used alone in the investigated concentrations does not affect HepG2 cell viability/proliferation. In vitro, GC inhibits the proliferation of liver carcinoma cells, the IC50 value has been 0.002 mg/mL. The use of ML in complex with GC can increase the cytotoxic activity of the composite by 8-10 %. The ML+GC+HER2 AB complexes caused the synergistic effect and an increase in the cytotoxic activity, compared with GC used alone, up to 18-20 %, while GC contents reduced to 0.008 mg/mL. The results of the studies indicate that the use of ML based on magnetite, gemcitabine, and antibody increases the effectiveness of the antitumor medicines with a significant reduction in their dose and, respectively, the toxicoallergic reactions of the body, and nanosized magnetite can be promising for the manufacture of magnetically sensitive adsorption materials for medical purposes, e.g. for detoxification of an organism after GC therapy.