Synthesis and Properties of Magnetically Sensitive Nanocomposites Based on Magnetite and Gemcitabine

The aim of the work is synthesis of new polyfunctional magnetosensitive nanocomposites (NC) capable of the targeted delivery in the tumors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma of a drug with chemotherapeutic mechanism of action gemcitabine (GC), and deposition with the help of magnetic field, investigation of the basic physico-chemical properties of NC. Research direction includes synthesis of nanosized one-domain magnetite as a magnetically sensitive carrier, modification of its surface by carbon covering with the aim of stabilization and chemical functionalization, biofunctionalization of NC by GC immobilization.

For investigation the following samples of NC were synthesized: Fe₃O₄, Fe₃O₄/HA, Fe₃O₄/C. The choice of samples is explained by the necessity to obtain a protective biocompatible cover with high adsorptive properties on a surface of magnetosensitive carrier. Carbonization of Fe₃O₄ surface and obtaining of Fe₃O₄/C NC was realized with the help of an organic substance – CS polygel (Carbomer 934).

Adsorption of GC on a surface of magnetite and Fe₃O₄/HA, Fe₃O₄/C NC was carried out in aqueous medium in the concentration range C₀ = 0.2–0.8 mg/L (g = 0.03 g, V = 5 mL, pH = 7.0) for 2 h in dynamic regime at room temperature. Amount of the adsorbed substance on a surface of NC was determined with the help of a spectrophotometer at λ = 268 nm from a calibration graph.

Adsorption characteristics were studied for surfaces of the synthesized NC with respect to GC. The results obtained show the dependence of adsorption capacity of the investigated samples on chemical nature of their surface. An increase in equilibrium GC concentration leads to a growth of adsorption capacity of Fe₃O₄/HA NC, which becomes almost in saturation for Fe₃O₄ and Fe₃O₄/C NC. The surfaces of NC researched are characterized by rather like values of adsorption parameters (A = 25–30 mg/g) which may be caused by similar nature of adsorption centers of their surfaces and adsorption mechanisms. GC extraction extent R (%) is 25–30%.

Magnetic properties of NC with adsorbed gemcitabine Fe₃O₄/GC, Fe₃O₄/HA/GC, Fe₃O₄/C/GC were investigated with the help of a laboratory vibration magnetometer. An idea of the investigations is based on the use of an ensemble of superparamagnetic carriers as a probe for determination of parameters and control of core-shell type nanostructures with complex composition. Hysteresis loops were measured for magnetite particles, and NC with immobilized GC. It has been determined by the magnetic granulometry methods that the thickness of GC shell in the composition of Fe₃O₄/GC NC is (2.4 ± 0.1) nm. Considering the thickness of GC layer is equal to 2.4 nm in all the studied nanostructures, we have found the value of thickness of hydroxyapatite layer in the structure of Fe₃O₄/HA/GC NC (3.5 ± 0.1 nm) and the thickness of C layer in Fe₃O₄/C/GC NC (3.2 ± 0.1 nm).

The obtained data may be useful in creation of medical magnetocarried nanosystems of targeted delivery and adsorptive materials for application in oncotherapy.