Magnetosensitive polyfunctional nanocomposites on the basis of magnetite and hydroxyapatite for their use in oncology

Abstract

The results of the research directed at the development of the concept of creating the magneto-sensitive nanocomposites (NC) with multilayered hierarchic nano-architecture of a core-shell type as well as with functions of biomedical nano-robots on the basis of a single-domain magnetite (Fe3O4), whose surface is modified by hydroxyapatite (HA) have been systemized and generalized. The nanostructures of this type are characterized by bio-adaptability with a person’s organism, deficiency of mutagenicity as well as by satisfactory magnetic characteristics from the point of view of the realization of the method of address delivery of medicines and local therapy.  Fe3O4 has been synthesized according to the method of neutralizing the salts of 2- and 3-valent Ferrum. The synthesized assemblages of nanoparticles (NP) of Fe3O4 were characterized by the limits of 3-23 nm. The average size of NP of Fe3O4 depended on synthesis conditions and equaled 8-15nm, the distribution according to their size could be done using technological methods. The specific surface of the magnetite was S = 90–180 м2/g, the samples for which S= ~ 110 м2 /g were used in process. By means of IR –spectra studies of the Fe3O4 surface, were discovered some functional groups of OH, the concentration of which was calculated on the data of thermo-gravimetric analysis and equaled 2.4 mM/g. The synthesis of HA membrane on Fe3O4 surface was performed using sol-gel method. The average crystals size of Fe3O4 and HA in the structure of NC Fe3O4/HA respectively equaled 15 and 19-21nm. By means of IR- spectra studies of Fe3O4/HA samples, groups of OH were discovered on the NC surface, their concentration was 2.2mM/g. The specific surface of NC Fe3O4 equaled Sп = 105 м2/g. Ca/P ratio was 1.6-1.7. The HA thickness on the Fe3O4 surface was estimated on Fe2p-/Fe3p-lines area to NC mass gain ratio and equaled ~4 nm. The processes of adsorption immobilization of chemotherapeutic preparations (cisplatin (CP), doxorubicin (DR)) as well as of normal immune globulin of a man (as a model of antibody-immune-therapeutic preparation) on NC surface have been studied.  Some significant adsorption activity related to CP complexes of nano-sized Fe3O4 has been discovered. Thus, under 298K for Fe3O4 the adsorption capacity Аmax = 80,1 mg/g, the removal coefficient R = 66,2 %. Fe3O4 modification by HA reduces the adsorption activity of NC surface related to CP:  Аmax = 54 mg/g, R = 64,8%. Perhaps, it occurs due to the decrease in the concentration of hydroxyl groups on NC surface of Fe3O4/HA as compared to the surface of initial Fe3O4. The period for establishing the absorption balance for NC surface of Fe3O4 /HA is within 10 min. The immune- globulin adsorption(Ig) was taking place in the medium of sodium chloride solution (SCS) for two hours in a dynamic regime under indoor temperature. The amount of adsorbed substance on the NC surface was determined by measuring the concentration of Ig in contact solutions before and after adsorption. The emitting of Ig in SCS was studied on Fe3O4/HА and on Fe3O4/HА/Ag samples which contain Ig immobilized from different buffer systems (phosphate buffer, physiological solution). The distribution coefficient (E) of immune globulin between the NC surface and the solution is 111,36 ml/g for Fe3O4/HА, and 186.67 ml/g for Fe3O4/HА/Ag. Under the adsorption from SCS for Fe3O4/HА Ε = 47, 2 ml/g, for Fe3O4/HА/Ag Е = 59,4 ml/g. The adsorption of Ig on the surface of NC from silver NP exceeds the adsorption on the surface of Fe3O4/HA in both buffer systems. It testifies to the fact that silver nano particles on the surface of a composite serve as additional adsorption centers. It has been determined that Ig emitting immobilized from SCS under high concentrations (A=17.38mg/g) practically does not occur.  The results of the experimental studies as to the NC effects on the cells lines MCF-7 of breast carcinoma of a man in vitro testify to the fact that t